Protein targeting or protein sorting is the mechanism by which a cell transports to the appropriate positions in the cell or outside of it. Both in prokaryotes and eukaryotes, newly synthesized proteins must be delivered to a specific sub-cellular location or exported from the cell for correct activity. This phenomenon is called protein targeting. Protein targeting is necessary for proteins that are destined to work outside the cytoplasm.This delivery process is carried out based on information contained in the protein itself. Correct sorting is crucial for the cell; errors can lead to diseases. In 1970, Günter Blobel conducted experiments on the translocation of proteins across membranes. He was awarded the 1999 Nobel Prize for his findings. He discovered that many proteins have a signal sequence, that is, a short amino acid sequence at one end that functions like a postal code for the target organelle.
This presentation gives an overview of Lipid Rafts, how it was discovered, its importance and the future research in this area,Feel free to comment and ask any questions
Protein targeting or protein sorting is the mechanism by which a cell transports to the appropriate positions in the cell or outside of it. Both in prokaryotes and eukaryotes, newly synthesized proteins must be delivered to a specific sub-cellular location or exported from the cell for correct activity. This phenomenon is called protein targeting. Protein targeting is necessary for proteins that are destined to work outside the cytoplasm.This delivery process is carried out based on information contained in the protein itself. Correct sorting is crucial for the cell; errors can lead to diseases. In 1970, Günter Blobel conducted experiments on the translocation of proteins across membranes. He was awarded the 1999 Nobel Prize for his findings. He discovered that many proteins have a signal sequence, that is, a short amino acid sequence at one end that functions like a postal code for the target organelle.
This presentation gives an overview of Lipid Rafts, how it was discovered, its importance and the future research in this area,Feel free to comment and ask any questions
The delivery of newly synthesized protein to their proper cellular destination, usually referred to as protein targeting or sorting.
The mode of protein transport depends chiefly on the location in the cell cytoplasm of the polysomes involved in protein synthesis.
There are two modes of protein sorting:-
1) Co - translational Transportation.
2) Post - translational Transportation.
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle.
More than half of all proteins interact with membranes.
Describes the plasma membrane in detail, explains the each major component with its functions.
Transport mechanism across the cell is covered with detailed explanation with examples.
by Dr. N.Sivaranjani, MD
Most bacteria are free-living organisms that grow by increasing
in mass and then divide by binary fission.
Growth and division are controlled by genes, the expression
of which must be regulated appropriately. Genes
whose activity is controlled in response to the needs of a
cell or organism are called regulated genes. All organisms
also have a large number of genes whose products
are essential to the normal functioning of a growing and
dividing cell, no matter what the conditions are. These
genes are always active in growing cells and are known as
constitutive genes or housekeeping genes; examples include
genes that code for the enzymes needed for protein
synthesis and glucose metabolism. Note that all genes are
regulated on some level. If normal cell function is impaired
for some reason, the expression of all genes, including
constitutive genes, is reduced by regulatory
mechanisms. Thus, the distinction between regulated
and constitutive genes is somewhat arbitrary.
Protein glycosylation and its associated disordersSaranya Sankar
Protein glycosylation and its associate disorders. Glycosylation is one of the post translational modifications important for the normal function of the protein such as cell adhesion, signalling etc.. defect in this process leads to fatal disorder such as cancer, PNH....
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations in the cell or outside it. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, plasma membrane, or to exterior of the cell via secretion.
The delivery of newly synthesized protein to their proper cellular destination, usually referred to as protein targeting or sorting.
The mode of protein transport depends chiefly on the location in the cell cytoplasm of the polysomes involved in protein synthesis.
There are two modes of protein sorting:-
1) Co - translational Transportation.
2) Post - translational Transportation.
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle.
More than half of all proteins interact with membranes.
Describes the plasma membrane in detail, explains the each major component with its functions.
Transport mechanism across the cell is covered with detailed explanation with examples.
by Dr. N.Sivaranjani, MD
Most bacteria are free-living organisms that grow by increasing
in mass and then divide by binary fission.
Growth and division are controlled by genes, the expression
of which must be regulated appropriately. Genes
whose activity is controlled in response to the needs of a
cell or organism are called regulated genes. All organisms
also have a large number of genes whose products
are essential to the normal functioning of a growing and
dividing cell, no matter what the conditions are. These
genes are always active in growing cells and are known as
constitutive genes or housekeeping genes; examples include
genes that code for the enzymes needed for protein
synthesis and glucose metabolism. Note that all genes are
regulated on some level. If normal cell function is impaired
for some reason, the expression of all genes, including
constitutive genes, is reduced by regulatory
mechanisms. Thus, the distinction between regulated
and constitutive genes is somewhat arbitrary.
Protein glycosylation and its associated disordersSaranya Sankar
Protein glycosylation and its associate disorders. Glycosylation is one of the post translational modifications important for the normal function of the protein such as cell adhesion, signalling etc.. defect in this process leads to fatal disorder such as cancer, PNH....
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations in the cell or outside it. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, plasma membrane, or to exterior of the cell via secretion.
This presentation aims to provide an overview of the mechanisms and key players involved in intracellular transport, highlighting their significance in cellular processes. Overview of Cellular Organization: Briefly describe the different compartments of a eukaryotic cell, including the nucleus, cytoplasm, endoplasmic reticulum, Golgi apparatus, mitochondria, and lysosomes. Emphasize that intracellular transport ensures the efficient distribution of components between these compartments.
The plasma membrane, also called the cell membrane, is the membrane found in all cells that separates the interior of the cell from the outside environment. . The plasma membrane consists of a lipid bilayer that is semipermeable. The plasma membrane regulates the transport of materials entering and exiting the cell.
In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
3. Introduction
•
It is the movement of the solutes and the vesicles within the cell
•
Eukaryotic cells transport packets of components (membrane‐bound
vesicles and organelles, protein rafts, mRNA, chromosomes)
•
Mechanism of movement is the attachment to molecular
motors that haul them along microtubules and actin filaments
•
This is distinct from intercellular transport, which deals solely with
the movement of cargo between cells not the net movement within a
cell
4. •
Intracellular transport involves the movement of various
components within the cells
•
Paracellular transport refers to the transfer of substances across
an epithelium by passing through the intercellular
space between the cells
•
Transcellular transport, where the substances travel through the
cell, passing through both the apical membrane and basolateral
membrane
5.
6. •
The cytoskeleton is key in intracellular transport as they provide
the mechanical support necessary for movement
•
Composed of actin, intermediate filaments and microtubules which
mediate locomotion, intracellular transport of organelles, cell shape
and chromosome separation
•
Intracellular transport is unique to eukaryotic cells as they possess
organelles enclosed in membranes
•
Conversely, in prokaryotic cells there is no need for this specialized
transport mechanism as there are no membranous organelles and
compartments to traffic between ( simple diffusion )
7. Protein Sorting
•
The process by which the proteins are transported to their
appropriate target in the cell or outside it
•
Proteins can be targeted to the inner space of an organelle, different
intracellular membranes, plasma membrane, or to exterior of the cell
via secretion
•
Many Proteins carry the signals that target them to their destinations
•
The signals are the fundamental component of the sorting system
•
Sorting decision made early in the process of biosynthesis
8.
9. Targeting Sequence or Compound Organelle targeted
Signal Peptide sequence Membrane of ER
Amino Terminal KDEL sequence Luminal surface of ER
Amino terminal sequence
( 70-residue region)
Mitochondria
NLS ( Eg. Pro-Lys-Ala-Lys-Val) Nucleus
PTS ( Eg : Ser-Lys-Leu) Peroxisome
Mannose 6 Phosphate Lysosome
10.
11. Mechanisms of Intracellular
Transport•
Nuclear Pores ( Nucleus )
•
Protein Translocators (ER, mitochondria,
chloroplasts, peroxisomes)
•
Vesicular Transport
( Lysosome , cell surface ,golgi )
12. Nuclear Pores
•
Nuclear pore complexes are large protein complexes spanning
the nuclear envelope
•
The proteins that make up the nuclear pore complex are known
as nucleoporins
•
About half of the nucleoporins typically contain solenoid protein
domains
•
This transport includes RNA and ribosomal proteins moving from
nucleus to the cytoplasm
13. •
The diameter of NPC is 9mm but can increase upto 28 mm
•
Molecules smaller than 28nm can pass through the NPC by
diffusion
•
Larger ones require special translocation mechanisms
•
The proteins to be imported carry a nuclear localization signal eg
Pro-Lys-Ala-Lys
•
Depending on the NLS it contains the cargo protein interacts with
the importins and the complex docks at the NPC
14. •
Another family of protein RAN comes into play and helps in the
translocation
•
Ran are the small monomeric nuclear GTPase and exist in either
GTP bound or GDP bound state
•
The GTP bound state of Ran is favored in the nucleus and the GDP
bound state is favored in the cytoplasm
•
The cargo molecules once released into the nucleus , the importins
again recirculate in the cytoplasm for another cargo molecule
15. •
The proteins similar to importins called exportins are involved in the
transport of macromolecules from the nucleus
•
Similar to NLS the cargo proteins to be exported carry NES
•
Ran protein is involved in the export of the cargo molecules from the
nucleus as well
16.
17.
18. Protein Translocators
•
Proteins moving from the cytosol into the ER, mitochondria,
chloroplasts, or peroxisomes
•
Protein movement is mediated by specialized proteins
termed protein translocators
•
Unlike passage through nuclear pores, translocation
requires unfolding or co-translational transport
19. Protein Translocation Into the
ER•
Translocation of the proteins into the ER is mainly guided by the
signal hypothesis
•
It was proposed by the Bolbel and Sabatini
•
Proteins synthesized on the membrane bound polyribosomes
contained a peptide extension called signal peptide
•
Responsible for mediating their attachment with the ER membrane
•
In contrast the protein being synthesized on the free polyribosomes
lack this signal peptide
22. •
Insertion of resident proteins into the ER is dependent on the specific signal
eg KDEL
•
But the membrane flow of certain proteins from the ER to the cell
membrane is designated as bulk flow as this transport is non selective ,
occurs without any targeting signal involved
•
But on the way back to the membrane if the proteins are destined to the
lysosme or the secretory vesicles , the movement is mediated by the
targeting sequence
ER
Cis
Golgi
Medial
Golgi
Trans
golgi
Lysosomes
Secretory
vesicles
23. Mitochondrial Protein Import
*
Most mitochondrial proteins are synthesized on cytoplasmic ribosomes
and are post-translationally imported into this organelle.
*
Because of the double membrane surrounding this organelle, there are
four targets for mitochondrial proteins:
1. Outer membrane 3. Inner membrane
2. Intermembrane space 4. Matrix space
*
Mitochondrial proteins usually contain an N-terminal targeting sequence
that is capable of forming an amphipathic -helix;
*
Positively-charged residues are clustered on one side of the helix and
uncharged residues are present on the other.
*
The mitochondrial outer membrane contains specific receptor proteins
that bind to the mitochondrial targeting signal.
26. *
Translocation into the mitochondrial matrix requires both ATP hydrolysis
and an electrochemical gradient across the inner mitochondrial
membrane.
*
Translocation occurs at sites where the inner and outer membrane are
in close apposition. These regions are known as contact sites.
*
Proteins are imported into the mitochondria in an unfolded state.
*
Maintenance in an unfolded state is mediated by hsp70 proteins that act
as molecular chaperones.
*
Protein transport into the inner membrane or intermembrane space
30. Vesicular Transport
•
Vesicular transport is the predominant mechanism for exchange of
proteins and lipids between membrane-bound organelles in
eukaryotic cells
•
This form of transport involves the movement of various elements
with the aid of the bubble like vesicles created from the cell
membrane
•
It is fundamentally divided into endocytosis and exocytosis
•
Endocytosis is divided into 3 distinct mechanisms : Phagocytosis ,
Pinocytosis and receptor mediated endocytosis
31.
32. Receptor Mediated Endocytosis
•
The major mechanism of vesicular transport between ER and Golgi
and also from trans golgi to the polyribosomes
•
Takes place in the regions of the membranes known as coated pits
•
The coated pits has high concentration of protein clarthrin and this
mechanism of receptor mediated endocytosis is the clarthin coated
vesicle method
•
However there is another method in which the receptor mediated
endocytosis takes place without the clarthin coated vesicles
33. •
At least four types of coated vesicles has been distinguished
•
Clarthin coated vesicles : Trans golgi to prelysosomes and from
plasma membrane to endosomes
•
COPI: Bi-directional transport from ER to golgi and in the reverse
•
COPII : From ER to golgi
34. Intracellular Transport 34
The pathway of vesicular transport
The endomembrane transport pathway
There are the 3 steps of vesicular transport
1) vesicle budding
2) targeting
3) fusion
Notice that there is transport in both
anterograde and retrograde directions
35.
36. Clathrin Independent Pathway
•
The pathway proposed by Rothman and colleagues
•
The pathway plays the major role in the anterograde transport of
proteins into the lysosome or the cell membrane from the ER
•
Each transport vesicle bears one specific target marker consisting of
one or more v-SNARE proteins
•
Each target membrane bears t-SNARE proteins with which the v-
SNARE proteins interact specifically
•
This pathway is complex and has been proposed to occur in
37. 8 Steps of Clathrin Independent
Transport Pathway
ü
Coat Assembly
ü
Recruitment of coat proteins
ü
Bud pinching off
ü
Coat disassembly
ü
Vesicle targeting
ü
Fusion
38.
39.
40. Rab Protein Family
•
Are small monomeric GTPase
•
Attached to cytosolic faces of membrane via geranyl geranyl chains
•
They attach in the GTP bound state
•
They mediate the fusion of v-SNARE and t-SNARE by displacing a
protein sec1
•
Rab and sec1 proteins regulates the speed of vesicle fusion by
opposing action
41. SNARE protein family
•
SNARE proteins — "SNAP" (Soluble NSF Attachment
Protein) REceptor" — are a large protein complex consisting of at
least 24 members in yeasts and more than 60 members in
mammalian cells
•
The primary role of SNARE proteins is to mediate vesicle fusion,
that is, the fusion of vesicles with their target membrane bound
compartments (such as a lysosome)
•
Are the machinery required for the membrane fusion
•
Vesicle SNARE and Target SNARE are two divisions
42. Botulinum Toxin
•
Most lethal toxin known
•
Most serious cause of food poisoning
•
One component of the toxin is a protease specific only to the
synaptobrevin
•
Thus by inhibiting the v-SNARE the release of acetylcholine into the
NMJ is halted
43. Brefeldin –A
§
An anti viral produced by fungus Penicillium brefeldianum
§
Prevents GTP from binding to ARF in the step 1 of the anterograde
pathway that Is the step of Coat assembly
§
So in the presence of this fungal metabolite the golgi apparatus
appears to disintegrate and fragments are lost
§
44. Disorders Related to
Intracellular Transport
Familial Hypercholesteremia
•
Familial hypercholesterolemia, FH (type II hyperlipoproteinemia) is
an autosomal dominant disorder
•
Results from mutations affecting the structure and function of the
cell-surface receptor that binds plasma LDLs (low density
lipoproteins) removing them from the circulation
•
The defects in LDL-receptor (LDLR) interaction result in lifelong
elevation of LDL-cholesterol in the blood
45. 1.Receptor null mutation ( lack of receptor synthesis in the ER
2.Defective intracellular transport to golgi apparatus
3.Defective extracellular ligand binding
4.Defective endocytosis
5. Failure to release LDL molecules inside the endosome
Another finding underlying autosomal dominant
46.
47.
48. Mucolipodosis
•
Mucolipidosis II (I-cell disease) and related milder disorders,
characterized by leakage of multiple lysosomal hydrolases from
cells
•
In these diseases, the activity of the Golgi enzyme N-
acetylglucosamine-1-phosphotransferase is missing, reduced or
altered
•
Inheritence is atosomal recessive
•
Not generating common phosphomannosyl recognition marker of
acid hydrolases
49. Clinical Features
§
Puffy eyelids with slight exophthalmia
§
Excessive prominence of the epicanthal folds
§
Depressed nasal bridge
§
Full cheeks exhibiting multiple fine telangiectasia
§
Gingival hyperplasia and alveolar enlargement with buried teeth
§
Thick tongue
§
Low birth weight
50. Hermansky-Pudlak syndrome
•
Exhibit defects in the generation of transport intermediates is
Hermansky-Pudlak syndrome (HPS), a cluster of diseases
characterized by defective biogenesis of lysosome-related
organelles
•
In HPS type 1 and types 3-8, the defects have been pinpointed to
subunits of three distinct protein assemblies: biogenesis of
lysosome-related organelles complex (BLOC) 1, BLOC2 and
BLOC3
•
Results in oculocutaneous albinism (decreased pigmentation),
bleeding problems due to a platelet abnormality (platelet storage
pool defect), and respiratory issues due to the pulmonary fibrosis
•
The clinical manifestations of the disease are due to the effect on
the lysosome related organelles (LROs) , ie : melanosomes, platelet
dense granuels ,MHC class II compartments
52. References
•
Harper’s Illustrated Biochemistry 26th edition.
•
Rink J, Ghigo E, Kalaidzidis Y, et al. Rab conversion as a
mechanism of progression from early to late
endosomes. Cell. 2005;122(5):735–49.
•
Prydz K, Dick G, Tveit H. How many ways through the Golgi
maze Traffic.
•
Mostov KE, Verges M, Altschuler Y. Membrane traffic in
polarized epithelial cells. Curr Opin Cell Biol. 2000;12(4):483–
90.