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Pengetahuan struktur, bentuk dan sintesa protein
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Pengetahuan struktur, bentuk dan sintesa protein

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Pengetahuan struktur, bentuk dan sintesa protein Pengetahuan struktur, bentuk dan sintesa protein Presentation Transcript

  • Building blocks of proteins are called Amino Acids.All proteins contain the elements Carbon, Hydrogen,Oxygen and Nitrogen. Amino Acids contain the -NH2 group which is called the amino group And the COOH group or the Carboxyl group. Amino Acids are defined by the side group or R-Group.
  •  The bond that holds amino acids together is called a peptide bond.  When two more amino acids are put together they become a polypeptide. The order in which amino acids are placed in the chain determines the structure of the protein. The structure of the protein determines the function of the protein.
  • From amino acids to protein: N-terminus terminates by an amino group Peptide bond Amino acid C-terminus terminates by a carboxyl groupA peptide: Phe-Ser-Glu-Lys (F-S-E-K)
  • The Shape of proteins: Occurs Spontaneously Native conformation determined by different Levels of structure
  • Non covalentinteractions involved in the shape of proteins
  • Four Levels of Structure Determine the Shape of ProteinsPrimary structureThe linear arrangement (sequence) of amino acids and the location of covalent (mostlydisulfide) bonds within a polypeptide chain. Determined by the genetic code.Secondary structurelocal folding of a polypeptide chain into regular structures including the helix,sheet, and U-shaped turns and loops.Tertiary structureoverall three-dimensional form of a polypeptide chain, which is stabilized by multiplenon-covalent interactions between side chains.Quaternary structure:The number and relative positions of the polypeptide chains in multisubunitproteins. Not all protein have a quaternary structure.
  • Primary Structure Pro-insulin is produced in the C-peptide Pancreatic islet cells Pro-insulin protein 65/66 30/31 Human: Thr-Ser-Ile Cow: Ala-Ser-Val Pig: Thr-Ser-Ile Chiken: His-Asn-Thr Insuline C-peptide + C peptide
  • Protein conformation: most of the proteins fold into only one stable conformation or native conformation More than 50 amino acids becomes a protein
  • Protein conformation: most of the proteins fold into only one stable conformation or native conformation More than 50 amino acids becomes a protein
  • SECONDARY STRUCTURE Stabilized by hydrogen bonds H- bonds are between –CO and –NH groups of peptide backbone H-bonds are either intra- or inter- molecular 3 types : a-helix, b-sheet and triple-helix Helix: helix conformation was discovered 50 years ago in keratineabundant in hair nails, and horns Sheet:discovered within a year of the discovery of helix. Found inprotein fibroin the major constituant of silk
  • The helix:result from hydrogen bonding, does not involve the side chain of the aminoacid
  • sheet:result from hydrogen bonding, does not involve the side chain of the amino acid
  • Two type ofSheet structures An anti paralellel sheet A paralellel sheet
  • TRIPLE HELIX  Limited to tropocollagen molecule  Sequence motif of –(Gly-X-Pro/Hypro)n-  3 left-handed helices wound together to give a right-handed superhelix  Stable superhelix : glycines located on the central axis (small R group) of triple helix  One interchain H-bond for each triplet of aas – between NH of Gly and CO of X (or Proline) in the adjacent chain Triple helix of Collagen
  • NONREPETITIVE STRUCTURES Helices/ -sheets: ~50% of regular 2ostructures of globular proteins Remaining : coil or loop conformation Also quite regular, but difficult to describe Examples : reverse turns, -bends (connect successive strands of antiparallel -sheets)
  • The Beta Turn (aka beta bend, tight turn)  allows the peptide chain to reverse direction  carbonyl O of one residue is H-bonded to the amide proton of a residue three residues away  proline and glycine are prevalent in beta turns (?)
  • -bulge A strand of polypeptide in a -sheet may contain an “extra” residue This extra residue is not hydrogen bonded to a neighbouring strand This is known as a -bulge.
  • Tertiary structure: the overall shape of a protein The secondary structure of a telephone cord A telephone cord, specifically the coil of a telephone cord, can be used as an analogy to the alpha helix secondary structure of a protein. The tertiary structure of a telephone cord The tertiary structure of a protein refers to the way the secondary structure folds back upon itself or twists around to form a three- dimensional structure. The secondary coil structure is still there, but the tertiary tangle has been superimposed on it.
  • Tertiary structure: the overall shape of a protein Full three dimensional organization of a protein  R-group interactions result in 3D structures of globular proteins  Types of interactions : H-, ionic- (salt linkage), hydrophobic- and disulphide- bond  Hydrophilic R groups on surface while hydrophobic R groups buried inside of molecule  Wide variety of 3o structures: since large variation in protein sizes and amino acid sequencesThe three-dimensional structure of a protein kinase
  • The role of side chain in the shape of proteins Hydrophili c Hydrophobic
  • A coiled-coil:Structure occurs when the 2 ahelix have most of their nonpolar(hydrophobic) side chains on oneside, so that they can twist aroundeach other with these side chainfacing inwards
  • Quaternery structure: If protein is formed as a complex of more than one protein chain, the complete structure is designed as quaternery structure:• Generally formed by non-covalent interactionsbetween subunits• Either as homo- orhetero-multimers
  • QUATERNARY STRUCTURE: ADVANTAGES Oligomers (multimers) are more stable than dissociated subunits  They prolong life of protein in vivo Active sites can be formed by residues from adjacent subunits/chains  A subunit may not constitute a complete active site Error of synthesis is greater for longer polypeptide chains Subunit interactions : cooperativity/ allosteric effects
  • Primary structureSecondary structureTertiary structureQuaternary structure
  • Protein domains:•Any part of a protein that can foldindependently into a compact, stablestructure. A domain usually contains between40 and 350 amino acids.• A domain is the modular unit from whichmany larger proteins are constructed.• The different domain of protein are oftenassociated with different functions.
  • Protein domains The NAD-bindingCytochrome b562 domain ofA single domain protein the enzyme lactic dehydrogenase The variable domaininvolved in electron transport of an immunoglobulinin mitochondria
  • Protein Folding is the physical process by which a polypeptide folds into its characteristic andfunctional three-dimensional structure from random coil.[1] Each protein exists asan unfolded polypeptide or random coil when translated from a sequenceofmRNA to a linear chain of amino acids.This polypeptide lacks any developed three-dimensional structure.Amino acids interact with each other to produce a well-defined three dimensionalstructure, the folded protein, known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence.For many proteins the correct three dimensional structure is essential tofunction. Failure to fold into the intended shape usually produces inactiveproteins with different properties including toxic prions.Several neurodegenerative and other diseases are believed to result from theaccumulation of misfolded (incorrectly folded) proteins.Many allergies are caused by the folding of the proteins, for the immune systemdoes not produce antibodies for certain protein structures.
  • Function of proteins• Enzymatic catalysis• Transport and storage (the protein hemoglobin, albumins)• Coordinated motion (actin and myosin).• Mechanical support (collagen).• Immune protection (antibodies)• Generation and transmission of nerve impulses - someamino acids act as neurotransmitters, receptors forneurotransmitters, drugs, etc. are protein in nature. (theacetylcholine receptor),• Control of growth and differentiation - transcription factorsHormones growth factors ( insulin or thyroid stimulatinghormone)
  • Enzymes  Enzymes are proteins that catalyze (i.e. speed up) chemical reactions. Enzymes are catalysts.  Enzymes work on things called Substrates  Each enzyme is specific for its substrate  Almost all processes in a cell need enzymes in order to occur at significant rates. Enzymes are not used up by the reaction. After they have done their work they release the products and are not changed Each enzyme can work on many molecules of the substrate
  • Lock and Key Model The method in which enzymes work is called the lock and key model
  • Transport and storage - small molecules are often carried by proteinsin the physiological setting (for example, the protein hemoglobin is responsiblefor the transport of oxygen to tissues). Many drug molecules are partially boundto serum albumins in the plasma. The binding of oxygen is affected by molecules such as carbon monoxide (CO) (for example from tobacco smoking, cars and furnaces). CO competes with oxygen at the heme binding site. Hemoglobin binding affinity for CO is 200 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduces hemoglobins ability to transport oxygen. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin. When inspired air contains CO levels as low as 0.02%, headache and nausea occur; if the CO concentration is3-dimensional structure of hemoglobin. increased to 0.1%, unconsciousness will follow. InThe four subunits are shown in red and heavy smokers, up to 20% of the oxygen-active sitesyellow, and the heme groups in green. can be blocked by CO.
  • Coordinated motion - muscle is mostly protein, and muscle contraction ismediated by the sliding motion of two protein filaments, actin and myosin. Platelet activation is a controlled sequence of actin filament: Severing Uncapping Elongating Cross linking That creates a dramatic shape change in the platelet Activated plateletPlatelet before activation Activated platelet at a later stage than C)
  • Mechanical support –skin and bone are strengthened by the protein collagen. Abnormal collagen synthesis or structure causes dysfunction of • cardiovascular organs, • bone, • skin, • joints • eyes Refer to Devlin Clinical correlation 3.4 p121
  • Immune protection - antibodies are protein structures that areresponsible for reacting with specific foreign substances in the body.
  • Generation and transmission of nerve impulses Some amino acids act as neurotransmitters, which transmit electrical signals from one nerve cell to another. In addition, receptors for neurotransmitters, drugs, etc. are protein in nature. An example of this is the acetylcholine receptor, which is a protein structure that is embedded in postsynaptic neurons. GABA: gamma Amino butyric acid Synthesised from glutamate GABA acts at inhibitory synapses in the brain. GABA acts by binding to specific receptors in the plasma membrane of both pre- and postsynaptic neurons. Neurotransmetter
  • Control of growth and differentiation -proteins can be critical to the control of growth, cell differentiation and expression ofDNA.For example, repressor proteins may bind to specific segments of DNA,preventing expression and thus the formation of the product of that DNAsegment.Also, many hormones and growth factors that regulate cell function, such asinsulin or thyroid stimulating hormone are proteins.
  •  DNA is found packed in the nucleus of eukaryotic organisms; it is found in the cytoplasm of prokaryotic organisms DNA is packed together and wrapped around special proteins called HISTONES DNA bound protein is called CHROMATIN When chromatin condenses (gets thicker) it forms CHROMOSOMES
  • NucleosomeChromosome DNA double helix Coils Supercoils Histones
  • DNA Structure  Double Helix - twisted ladder  Made up of monomers called nucleotides  Nucleotides are composed of:  Deoxyribose sugar  Phosphate group  Nitrogenous base
  • Nitrogenous Bases  Two types:  Purines (two rings)  Pyrimidines (one ring)  Purines  Adenine and Guanine  Pyrimidines  Thymine and Cytosine
  • Purines Pyrimidines Adenine Guanine Cytosine ThyminePhosphate Deoxyribosegroup
  • BondingTEMPLATE STRAND A C G G T A T G C C A T Weak HYDROGEN bonds form between the Nitrogen Base Pairs.
  • Chargaff’s rules: Base pairing rule is A-T and G-C Thymine is replaced by Uracil in RNA Bases are bonded to each other by Hydrogen bonds Discovered because of the relative percent of each base; (notice that A-T is similar and C-G are similar)
  • DNA StructureBackbone alternates with phosphate & sugr/deoxyriboeswith the nucleotides forming the rungs or steps of the ladder
  • The backbone of it all…TEMPLATE STRAND A C G G T A T G C C A T The backbone is made of alternating sugars and phosphates. - Remember: Sugar ALWAYS attaches to the Nitrogen base
  • Decoding the Information in DNA How does DNA (a twisted latter of atoms) control everything in a cell and ultimately an organism?  DNA controls the manufacture of all cellular proteins including enzymes  A gene is a region of DNA that contains the instructions for the manufacture of on particular polypeptide chain (chain of amino acids) DNA is a set of blueprints or code from making proteins
  • Genetic Code Genetic code – the language of mRNA instructions (blueprints) Read in three letters at a time Each letter represents one of the nitrogenous bases: A, U, C, G Codon found on mRNA; consists of three bases (one right after the other) 64 codons for 20 amino acids
  • Codon (cont’d) For example, consider the following RNA sequence: UCGCACGGUThe sequence would be read three base pairs at a time: UCG – CAC – GGUThe codons represent the amino acids: Serine – Histidine – Glycine AUG – start codon or Methionine UAA, UAG, UGA – stop codons; code for nothing; like the period at the end of a sentence
  • The gene-enzyme relationship has been revised to the one-gene, one-polypeptide relationship.Example: In hemoglobin, each polypeptide chain is specified by a separate gene.Other genes code for RNA that is not translated to polypeptides; some genes are involved in controlling other genes.
  • DNA & RNA Before mitosis (during S phase of interphase) , acomplete copy of a cell’s DNA is made through a processcalled replication. When a cell divides, each daughter cell gets onecomplete copy of the DNA.  Similar to photocopying a document – the end result is two identical documents that contain the same information. Now that we know something about DNA’s structure,lets look at how it replicates.
  • Steps of DNA Replication1) DNA must unwind and break the hydrogen bonds2) Each strand is used as a template (blueprint)3) Two new strands of DNA are formed from the original strand by the enzyme DNA Polymerase
  • DNATranscription
  •  During replication, an enzyme called helicase “unzips” theDNA molecule along the base pairing, straight down themiddle. Another enzyme, called DNA polymerase, moves along thebases on each of the unzipped halves and connectscomplementary nucleotides.
  • From Gene to Protein Synthesis of DNA from RNA is reverse transcription. Viruses that do this are Retroviruses.
  • Differences between DNA and RNA DNA RNA  Structure:  Structure:  Double stranded  Single-stranded  Sugar: Deoxyribose  Sugar: Ribose Bases: Bases:  Adenine  Adenine  Guanine  Guanine  Cytosine  Cytosine  Thymine  Uracil
  • ow do you get from DNA to Proteins? TRANSCRIPTION – the synthesis of RNA under the direction of DNA TRANSLATION – the actual synthesis of a protein, which occurs under the direction of mRNA
  • Splicing Each gene has it own promotor Each gene is widely spacied The information is fragmented Exon = expressed gen Intron = intervening partAlternative splicing: A regulatory mechanism by whichvariations in the incorporation of a gene’s exons, or codingregions, into messenger RNA lead to the production of morethan one related protein, or isoform.Alternative splicing is a source of genetic diversity ineukaryotes.Splicing has been used to account for the relatively smallnumber of genes in the human genome.
  • mRNA Splicing The entire gene is transcripted into a message. Some of the message is Junk (introns) and is removed before exiting the nucleus. A spliceosome is a complex of specialized RNA and protein that removes introns from a pre-mRNA This process is generally referred to as splicing.Introns typically have a ―GU‖ nucleotide sequence at the 5 endsplice site, and an AG at the 3 end splice site.
  • Guttmacher and Collins , NEJM, 347 (19): 1512, Figure 2 November 7, 2002
  • Translation- the Ultimate Goal!•Going from mRNA to the final product
  • Transcription- how RNA is made Just as DNA polymerase makes new DNA, a similarenzyme called RNA polymerase makes new RNA. RNA polymerase temporarily separates the strands of asmall section of the DNA molecule. This exposes some ofthe bases of the DNA molecule. Along one strand, the RNA polymerase bindscomplementary RNA nucleotides to the exposed DNAbases. An exposed thymine on the DNA strand hooks up withan RNA nucleotide with an adenine; an exposed cytosineon the DNA hooks up with an RNA nucleotide with aguanine base; an exposed adenine DNA base will hook upwith URACIL!
  •  As the RNA polymerase moves along, it makes astrand of messenger RNA (mRNA). It is called messenger RNA because it carries DNA’smessage out of the nucleus and into the cytoplasm. mRNA is SINGLE STRANDED! When the RNA polymerase is done reading the genein the DNA, it leaves. The separated DNA strands reconnect, ready to beread again when necessary. mRNA moves out of the nucleus and finds a ribosome On the ribosome, amino acids are assembled to formproteins in the process called translation.
  • Translation: Protein Synthesis1)mRNA is transcribed in the nucleus and leaves the nucleus to the cytoplasm2) mRNA attaches to the ribosome3) tRNA carries the anticodon which pairs up with the codon on the mRNA4) tRNA brings the correct amino acid by reading the genetic code5) The amino acids are joined together to form a polypeptide (protein)6) When a stop codon is reached (UAA, UAG, UGA) protein synthesis stops
  • TranslationmRNA GUA UCU GUU ACC GUA•mRNA carries the same message as DNA butrewritten with different nitrogen bases.•This message codes for a specific sequence ofamino acids•Review..Amino acids are the building blocksof… •PROTEINS
  • SO: Say the mRNA strand reads:  mRNA (codon) AUG–GAC–CAG-UGA  tRNA (anticodon) UAC-CUG-GUC-ACU tRNA would bring the amino acids: Methionine-Aspartic acid-Glutamine-stop
  • TranslationmRNA GUA UCU GUU ACC GUA•Codon: a sequence of 3 nitrogen bases onmRNA that code for 1 amino acid •It’s a TRIPLET code•Example: This strand of mRNA has 5codons, so it would code for 5 amino acids.
  • TranslationmRNA GUA UCU GUU ACC GUA •These codons are universal for every bacteria, plant and animal on earth •There are 64 codons which code for all 20 amino acids on earth.
  • The genetic code: specifies which amino acids will be used to build a proteinCodon: a sequence of three bases. Each codon specifies a particular amino acid.Start codon: AUG—initiation signal for translationStop codons: stops translation and polypeptide is released
  • Codons matchup withanticodons tocreate aprotein
  • Figure 12.6 The Genetic Code
  • Translation mRNA GUA UCU GUU ACC GUA Ribosome•The mRNA molecule travels to the ribosomeswhere the mRNA codes are ―read‖ by theribosomes•Ribosomes hold the mRNA so another typeof RNA, transfer RNA (tRNA) can attach to themRNA
  • TranslationmRNA GUA UCU GUU ACC GUA Ribosome CA U AG A
  • TranslationmRNA GUA UCU GUU ACC GUA CA U A G A CA A
  • Elements of translation Ribosomes rRNA Large and small subunits  Initiation Codons  Chain Elongation Initiator or start codon  Peptide bonds Methionine (AUG)  Chain termination Stop codons  Polysome tRNA
  • RNARibonucleic acidSingle-stranded helixSugar is riboseThymine is replaced by URACIL
  • Major RNAsmRNAmessenger RNA carries the genetic information that will beexpressed ultimately as proteins. (carries information fromDNA to ribosome)tRNAtransfer RNA is the adapter molecule. It recognizes the codonsof the mRNA on the one hand, and it can be covalently bondedto the appropriate amino acid, on the other. (Carries aminoacids)rRNAribosomal RNA is found in the ribosomes (Makes upribosomes)
  • RNA-Coding GenesA. Ribosomal RNA (rRNA) genesB. Transfer RNA (tRNA) genesC. Small Nuclear RNA (snRNA) genesD. Small Nucleolar RNA (snoRNA) genesE. Regulatory RNA genesF. XIST RNA-Coding GenesG. MicroRNA (miRNA) genesH. Antisense RNA genesI. Riboswitch genes
  • RNA can be Transfer Messenger Ribosomal RNA RNA RNAalso called which functions to also called which functions to also called Bring Combine Carry rRNA tRNA amino mRNA with proteins instructions acids to ribosome from to to make up DNA Ribosome Ribosomes
  • Processing the RNA transcript into mRNA 1. Mono-cistronic 2. Maturation a) RNA capping b) RNA polyadenylation c) RNA splicing Cistron = Gene
  • Maturation of Eukatriotic mRNA Intron: not founded in cytoplasmCap: 7-Methyl-Guanosine cap, protect mRNAfrom degradation and serve as a ribosomebinding sitePoly-A tail: AAUAAA (200 A’s) to protect themessage from degradation Splicing: remove of intronsLariat structures: introns removed from hnRNA(heterogeneus nuclear RNA) are degraded innucleus
  • Transfer RNA
  • The conformation (three-dimensional shape) of tRNA results from base pairing (H bonds) within the molecule.3 end is the amino acid attachment site—binds covalently. Always CCA.Anticodon: site of base pairing with mRNA. Unique for each species of tRNA.
  • Hydrogen bonds form between the anticodon of tRNA and the codon of mRNA.Small subunit rRNA validates the match—if hydrogen bonds have not formed between all three base pairs, it must be an incorrect match, and the tRNA is rejected.
  • Example: DNA codon for arginine: 3-GCC-5 Complementary mRNA: 3-CGG-5 Anticodon on the tRNA: 3-GCC-5 This tRNA is charged with arginine.TAC - ___ ____ ____ - TAC
  • Wobble: specificity for the base at the 3 end of the codon is not always observed.Example: codons for alanine—GCA, GCC, and GCU—are recognized by the same tRNA.
  • Protein formation Amino acids link together to form a protein The new protein could become cell part, an enzyme, a hormone etc.
  • Ribosomic RNA 50SProkaryotic ribosomeshave 3 rRNAmolecules:23S, 16S and 5S. 30S2 Subunits: 50S+30SEukaryotic ribosomeshave 4 rRNA 60Smolecules:28S, 18S, 5.8S and 5S2 Subunits: 60S+40S 40S
  • Ribosome: the workbench—holds mRNA and tRNA in the correct positions to allow assembly of polypeptide chain.Ribosomes are not specific, they can make any type of protein.
  • ProkaryotesSmall Subunit 30s Large subunit 50s16s 5s21 proteins 23s 34 proteinsEukaryotes:Small 40S Large 60S 5S18S 28S33 proteins 5.8S 49 proteins**The numbers are not additive – based on centrifugation rates
  • Subunits are held together by ionic and hydrophobic forces (not covalent bonds).When not active in translation, the subunits exist separately.
  • Figure 12.10 Ribosome Structure
  • Large subunit has three tRNA binding sites:• A site binds with anticodon of charged tRNA.• P site is where tRNA adds its amino acid to the growing chain.• E site is where tRNA sits before being released.
  • RNA polymerases catalyze synthesis of RNA.RNA polymerases are processive—a single enzyme-template binding results in polymerization of hundreds of RNA bases.
  • Figure 12.4 RNA Polymerase What are the bonds called that form between ribose bases?
  • Transcription occurs in three phases:• Initiation• Elongation• Termination http://vcell.ndsu.edu/animations/transcription/movie.htm
  • Initiation requires a promoter—a special sequence of DNA.RNA polymerase binds to the promoter.Promoter tells RNA polymerase where to start, which direction to go in, and which strand of DNA to transcribe.Part of each promoter is the initiation site.
  • DNA Is Transcribed to Form RNA (A)
  • http://www.biostudio.com/demo_freeman_pro tein_synthesis.htmSTEP 1Step 2
  • Start codon is AUG; first amino acid is always methionine, which may be removed after translation.The large subunit joins the complex, the charged tRNA is now in the P site of the large subunit.
  • Elongation: RNA polymerase unwinds DNA about 10 base pairs at a time; reads template in 3 to 5 direction.The RNA transcript is antiparallel to the DNA template strand.RNA polymerases do not proof read and correct mistakes.
  • Elongation: the second charged tRNA enters the A site.Large subunit catalyzes two reactions:1. Breaks bond between tRNA in P site and its amino acid.2. Peptide bond forms between that amino acid and the amino acid on tRNA in the A site.
  • Termination: specified by a specific DNA base sequence.Mechanisms of termination are complex and varied.Eukaryotes—first product is a pre-mRNA that is longer than the final mRNA and must undergo processing.
  • Termination: translation ends when a stop codon enters the A site.Stop codon binds a protein release factor—allows hydrolysis of bond between polypeptide chain and tRNA on the P site.Polypeptide chain—C terminus is the last amino acid added.
  • Table 12.1
  • Several ribosomes can work together to translate the same mRNA, producing multiple copies of the polypeptide.A strand of mRNA with associated ribosomes is called a polyribosome or polysome.
  • Figure 12.14 A Polysome (Part 1)
  • Figure 12.14 A Polysome (Part 2)
  • Stabilizing the message Posttranslational aspects of protein synthesis: 1. 5’ cap added to N side of new protein How is a message (mRNA) stabilized to get enough protein…at the right time?
  • 5’ cap can enhance translation – go faster
  • 2. Polyadenylation is the synthesis of a poly(A) tail, a stretchof adenines at the end of the mRNA molecule.At the end of transcription the last 3’ bit of the newly madeRNA is cleaved off by a set aof enzymes. The enzymes thensynthesize the poly(A) tail at the RNAs 3 end.The poly(A) tail is important for the nuclear export, translationand stability of mRNA. The tail is shortened over time andwhen it is short enough, the mRNA is degraded.In a few cell types, mRNAs with short poly(A) tails are storedfor later activation
  • Processing the protein (product) 3. TARGETING: Polypeptide may be moved from synthesis site to an organelle, or out of the cell. Amino acid sequence also contains a signal sequence—an ―address label.‖ i.e. – proteins targeted to ER 5-10 hydrophobic amino acids on the N-terminus.
  • Destinations for Newly Translated Polypeptides in a Eukaryotic Cell
  • A Signal Sequence Moves a Polypeptide into the ER (Part 1)
  • Figure 12.16 A Signal Sequence Moves a Polypeptide into the ER (Part 2) Folding chaperones (proteins) in RER fold proteins appropriately. Mis-folding diseases: Altzheimer’s Creutzfeld–Jakob disease (CJD) (prion disease) P53 – cancer from misfolded ―watchdog‖
  • What Happens to Polypeptides after Translation? 4. Glycosylation: addition of sugars to form glycoproteins Sugars may be added in the Golgi apparatus—the resulting glycoproteins end up in the plasma membrane, lysosomes, or vacuoles. Diseases: incorrect addition of sugars to specific amino acids – shows in infancy- almost always involves nervous system development.
  •  All proteins inserted into or associated with the cell membrane have sugars attached to them. They aid in recognition of other molecules. What would be some consequences of incorrect glycosylation at the cell membrane?
  • What Happens to Polypeptides after Translation? Protein modifications: 5. Proteolysis: cutting the polypeptide chain by proteases. Degradation of protein message. 6. Phosphorylation: addition of phosphate groups by kinases. Charged phosphate groups change the conformation. Generally makes protein into enzymes!
  • Posttranslational Modifications of Proteins