Chaperones are a functionally related group of proteins that assist the covalent folding or unfolding and the assembly or disassembly of other macromolecular structures.
RNA Polymerase
Introduction
Purification
History
PRODUCTS OF RNAP
Messenger RNA
Non-coding RNA or "RNA genes
Transfer RNA
Ribosomal RNA
Micro RNA
Catalytic RNA (Ribozyme)
prokaryotic and eukaryotic
Transcription by RNA Polymerase
TYPES OF RNA POLYMERASE
Type I
Type II
Type III
Prokaryotic Transcription Unit
EXPRESSION OF A PROKARYOTIC GENE
Prokaryotic Polycistronic Message Codes for Several Different Proteins
Eukaryotic Transcription Unit
ENHANCERS AND SILENCERS
RESULT OF THE TRANSCRIPTION CYCLE
RNAP III TRANSCRIBES HUMAN MICRORNAS
RNAP I–specific subunits promotepolymerase clustering to enhance the rRNA genetranscription cycle
RNAP II–TFIIB STRUCTURE ANDMECHANISM OF TRANSCRIPTION INITIATION
FIVE CHECKPOINTS MAINTAINING THE FIDELITY OFTRANSCRIPTION BY RNAP IN STRUCTURAL ANDENERGETIC DETAILS
RNA Polymerase
Introduction
Purification
History
PRODUCTS OF RNAP
Messenger RNA
Non-coding RNA or "RNA genes
Transfer RNA
Ribosomal RNA
Micro RNA
Catalytic RNA (Ribozyme)
prokaryotic and eukaryotic
Transcription by RNA Polymerase
TYPES OF RNA POLYMERASE
Type I
Type II
Type III
Prokaryotic Transcription Unit
EXPRESSION OF A PROKARYOTIC GENE
Prokaryotic Polycistronic Message Codes for Several Different Proteins
Eukaryotic Transcription Unit
ENHANCERS AND SILENCERS
RESULT OF THE TRANSCRIPTION CYCLE
RNAP III TRANSCRIBES HUMAN MICRORNAS
RNAP I–specific subunits promotepolymerase clustering to enhance the rRNA genetranscription cycle
RNAP II–TFIIB STRUCTURE ANDMECHANISM OF TRANSCRIPTION INITIATION
FIVE CHECKPOINTS MAINTAINING THE FIDELITY OFTRANSCRIPTION BY RNAP IN STRUCTURAL ANDENERGETIC DETAILS
Folding depends upon sequence of Amino Acids not the Composition. Folding starts with the secondary structure and ends at quaternary structure.
Denaturation occur at secondary, tertiary & quaternary level but not at primary level.
An Overview...
Definition of Translation.
Def. of Eukaryotes.
Translation: An Overview.
Components of Translation.
Some Enzymes .
Ribosome Role.
Mechanism of Translation.
Initiation.
Scanning Model of Initiation.
Initiation Factors.
Animation.
Elongation.
Chain Elongation: Translocation.
Animation.
Termination.
Animation....
It's not perfect still... what are your views friends?
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.
I have tried to make a precise presentation on protein transport, targeting and sorting into organelle's other than nucleus. Hope this might help you. Comments are welcome.
Post translation modifications(molecular biology)IndrajaDoradla
description of post translation modifications which include folding,proteolytic clevage and chemical modification and protein splicing and protein degradation
Folding depends upon sequence of Amino Acids not the Composition. Folding starts with the secondary structure and ends at quaternary structure.
Denaturation occur at secondary, tertiary & quaternary level but not at primary level.
An Overview...
Definition of Translation.
Def. of Eukaryotes.
Translation: An Overview.
Components of Translation.
Some Enzymes .
Ribosome Role.
Mechanism of Translation.
Initiation.
Scanning Model of Initiation.
Initiation Factors.
Animation.
Elongation.
Chain Elongation: Translocation.
Animation.
Termination.
Animation....
It's not perfect still... what are your views friends?
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.
I have tried to make a precise presentation on protein transport, targeting and sorting into organelle's other than nucleus. Hope this might help you. Comments are welcome.
Post translation modifications(molecular biology)IndrajaDoradla
description of post translation modifications which include folding,proteolytic clevage and chemical modification and protein splicing and protein degradation
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritance.
Retinal Pigment epithelial cells perform a multitude of functions to protect the retina and maintain normal vision. Any kind of RPE malfunction leads to a variety of ocular diseases.
This PPT explains the various functions performed by RPE to maintain normal vision.
Prokaryotic cells do not contain nuclei or other membrane-bound organelles.
The nucleoid is the area of a prokaryotic cell in which the chromosomal DNA is located.
Chromosome is several orders of magnitude larger than the cell itself.
So, if bacterial chromosomes are so huge, how can they fit comfortably inside a cell—much less in one small corner of the cell?
Most prokaryotes do not have histones (except some species of Archaea).
Thus, one way prokaryotes compress their DNA into smaller spaces is through supercoiling.
Most bacterial genomes are negatively supercoiled during normal growth.
Multiple proteins act together to fold and condense prokaryotic DNA.
One most abundant protein HU, found in the nucleoid, works with topoisomerase I to bind DNA and introduce sharp bends in the chromosome, Generating the tension necessary for negative supercoiling.
Recent studies… other proteins like integration host factor (IHF), can bind to specific sequences within the genome and introduce additional bends.
The folded DNA is then organized into a variety of conformations that are supercoiled and wound around tetramers of the HU protein, much like eukaryotic chromosomes are wrapped around histones.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
6. The chaperones are
concerned primarily
with protein folding
Some chaperones are
non-specific, and
interact with a wide
variety of polypeptide
chains, but others are
restricted to specific
targets.
7. Location
• In humans mostly in Endoplasmic reticulum
• General chaperones: GRP78/BiP, GRP94,
GRP170.
• Lectin chaperones: calnexin and calreticulin
• Non-classical molecular chaperones: HSP47 and
ERp29
• Folding chaperones:
• Protein disulfide isomerase (PDI)
• Peptidyl prolyl cis-trans-isomerase (PPI)
• ERp57
8. The term
`molecular
chaperone`
appeared first in
the literature in
1978
Invented
by Ron
Laskey
History
To describe the
ability of a
nuclear protein
called
‘Nucleoplasmin’
It prevented the
aggregation of folded
histone proteins with
DNA during the
assembly of
nucleosomes
9. • Later extended by R. John Ellis in 1987
o to describe proteins that mediated the post-
translational assembly of protein complexes.
• In 1988, realised that similar proteins mediated this
process in both prokaryotes and eukaryotes.
• Details were determined in 1989, when the ATP-
dependent protein folding was demonstrated in vitro.
10. Properties of chaperones
Molecular
chaperones interact
with unfolded or
partially folded
protein subunits e.g.
nascent chains
emerging from the
ribosome, or
extended chains
being translocated
across subcellular
membranes.
They stabilize non-native
conformation and facilitate
correct folding of protein
subunits.
They do not interact
with native proteins, nor
do they form part of the
final folded structures.
11. • Some chaperones are non-specific, and interact
with a wide variety of polypeptide chains, but
others are restricted to specific targets.
• They often couple ATP binding/hydrolysis to the
folding process.
• Essential for viability, their expression is often
increased by cellular stress.
12. As heat shock proteins
Heat shock
proteins (HSP)
are a family of
proteins that are
produced by
cells in response
to exposure to
stressful
conditions
Several heat
shock proteins
function as
intra-cellular
chaperones for
other proteins
In bacteria like
E. coli,
chaperones are
highly expressed
under high
stress e.g high
temperatures.
13. For this reason, the term "heat shock protein" has
historically been used to name these chaperones.
The prefix "Hsp" designates that the protein is
a heat shock protein.
The reason for this behaviour is that
protein folding is severely affected by
heat and therefore, some chaperones
act to prevent or correct damage
caused by misfolding.
14. Functions of chaperones
• They act as a container for the folding of other protein sub
units as they are called heat-shocked proteins.
• They also prevent the degradation of proteins in spinal stress
conditions.
• Some chaperone systems work as foldases . They support the
folding of proteins in an ATP-dependent manner .(for
example, in the GrpE or the DnaK /DnaJ /GrpE system).
15. • Other chaperones work as holdases . They bind folding
intermediates to prevent their aggregation, for example DnaJ
or Hsp33.
• Chaperones work in coordination by forming assemblies .
• Such assembly chaperones, especially in the nucleus are
concerned with the assembly of folded subunits into oligomeric
structures.
• The first protein to be called a chaperone assists the assembly
of nucleosomes from folded histones and DNA .
16. • They recognize and correct mistakes in folding by
binding to the non polar surface.
• Promote correct folding of their substrate proteins
by unfolding incorrect polypeptide chain
conformations.
• Providing an environment in which correct protein
folding can occur.
17. Macromolecular crowding
• The crowded environment of the cytosol can accelerate the
folding process.
• As a compact folded protein will occupy less volume than an
unfolded protein chain.
• Crowding can reduce the yield of correctly folded protein by
increasing protein aggregation.
• Crowding may also increase the effectiveness of the chaperone
proteins such as Grp E which could counteract this reduction
in folding efficiency.
18.
19. Cell homeostasis
• Two opposite functions
I. Protein folding
II. Degradation.
• The two processes
Are carried out through the transient formation of
complexes
Between different chaperones and co-chaperones
20. Transport across membranes
Across membranes of the mitochondria
Endoplasmic reticulum (ER).
Bacterial translocation—specific chaperone
a. maintains newly synthesized precursor polypeptide
chains in a translocation-competent state
b. and guides them to the translocon.
21. New functions for
chaperones
continue to be
discovered, such
as
a) Assistance in protein degradation
b) Bacterial adhesion activity
c) In responding to diseases linked to protein
aggregation and cancer maintenance.
22. They prevent inappropriate association or aggregation of
exposed hydrophobic surfaces
Direct their substrates into productive
folding
Transport or degradation pathways
Main Role
23. The type I interamolecular chaperones
• First discovered based on the studies on subtilisin, an
alkaline serine protease from bacillus subtilis.
• Mediate the folding of proteins
into their respective tertiary
structures and are mostly produced
as the N-terminal sequence extension.
24. • Mediate the formation of the quaternary or functional
structure of proteins
• Usually located at the
C-terminus of the protein
Type II intramolecular
chaperones
25. Mutations in the intramolecular chaperones can cause misfolding
of the functional domain,
results in distortion of their function leading
to human diseases.
26. Families
• Many families present in eukaryotes and prokaryotes
• Perform many similar and specific functions by
working in coordination systems
• Most common are hsp 70 and hsp 60 families
27. Small heat shock
proteins (hsp25)
[holders]
Hsp25 is the second
largest of 16
identifiable small heat
shock proteins in the
nematode.
Protect against
cellular stress
Prevent aggregation
in the lens (cataract)
Hsp90 ATPase [holder]
Hsp90 is a specialized
chaperone that assists
in the maturation of
client proteins.
These proteins
include over a hundred
transcription factors
and kinases, such as
steroid receptors
28. Hsp90
• Hsp90 (HtpG in E. coli) may be the least understood chaperone
• The exact function of Hsp90 is also currently a mystery. Researchers
don't know what it does in the maturation of its client proteins.
• They have discovered that it acts as part of a large complex of different
chaperone proteins.
• Some of these chaperones deliver immature proteins to the complex,
and others assist with folding.
• essential for activating many signalling proteins in the eukaryotic cell
• Each Hsp90 has an ATP-binding domain, a middle domain, and a
dimerization domain
29. Hsp90 (blue) and cochaperone Sba1 (green), with
bound ATP (red).
30. Calnexin , calreticulin
Calnexin (CNX) is a 67kDa integral protein of the
endoplasmic reticulum (ER)
• Calreticulin also known as calregulin in humans is
encoded by the CALR gene.
• Calreticulin is a multifunctional protein that binds
Ca2+ ion rendering it inactive
31. Hsp100 (Clp) ATPase [unfolder]
• The HSP100/Clp proteins are a newly discovered
family, promotion of proteolysis of specific cellular
substrates and regulation of transcription.
• Common ability is to disassemble higher-order protein
structures
32. Hsp100
• Hsp100 (Clp family in E. coli) proteins have been
studied in vivo and in vitro
• Ability to target and unfold tagged and misfolded
proteins.
• Form large hexameric structures
• Unfoldase activity in the presence of ATP.
33. Proteins in the Hsp100/Clp family form large hexameric
structures with unfoldase activity in the presence of
ATP.
These proteins are thought to function as chaperones
by processively threading client proteins through a
small 20 Å (2 nm) pore
Gives each client protein a second chance to fold.
Forms complexes that are responsible for the targeted
destruction of tagged and misfolded proteins.
34. Hsp 104
• Hsp104 = the Hsp100 of Saccharomyces cerevisiae
• Essential for the propagation of many yeast
prions.
• Deletion of the HSP104 gene results in cells that
are unable to propagate certain prions.
35. Hsp70 chaperones
• Their size is approximately 70,000 daltons
• Best characterized small (~ 70 kDa) chaperone
• Often work in concert with one or more smaller co-
chaperone proteins, which serve to modulate the activity
of the chaperone
• The Hsp70 proteins are aided by Hsp40 proteins (DnaJ in
E. coli), which increase the ATP consumption rate and
activity of the Hsp70s
37. • Hsp70 consists of ATP-binding N-terminal domain and
peptide binding C-terminal domain.
• ATP hydrolysis switches off and on the binding ability of C-
terminal domain.
• A special hydrophobic groove formed by α-helices and β-
strands provides the docking site
• For hydrophobic segments of misfolded proteins
38. • Hsp70s crowd around an unfolded substrate, stabilizing it
and preventing aggregation
• Until the unfolded molecule folds properly, at which time the
Hsp70s lose affinity for the molecule and diffuse away
• Hsp70 also acts as a mitochondrial and chloroplastic
molecular chaperone in eukaryotes
• Increased expression of Hsp70 proteins in the cell results in a
decreased tendency toward apoptosis.
39.
40. Hsp 60
also called "chaperonins" are barrel-shaped
structures
Composed of fourteen to sixteen subunits of proteins
that are approximately 60,000 daltons in size
The best characterized large (~ 1 MDa) chaperone
complex
41. Each subunit has a patch of non-polar amino acid groups
lining the inner surface of the barrel
This patch recognizes the exposed non-polar amino acids
of misfolded proteins.
The binding and hydrolysis of ATP triggers
conformational changes within the barrel
42.
43. • Most extensively studied Hsp60 chaperones include
• GroEL and GroES from E. coli
• TRiC/CCT from eukaryotic cells
• TRiC/CCT recognizes a much smaller set of proteins,
and appears to play an additional role in the assembly
of multiprotein complexes
44. GroEL is a
double-ring
14mer with a
hydrophobic
patch at its
opening
GroES is a single-
ring heptamer that
binds to GroEL in
the presence of
ATP or ADP
GroEL and
GroES forms a
well understood
complex
45. GroEL and GroES complex
• GroEL chaperone consists of two rings – cis (or proximal)
upper ring and trans (or distal)lower ring.
• GroES co-chaperone binds to both GroES rings
• Each of the GroEL rings consists of seven identical units
shown in the lower
• The units are arranged in a circular manner and form a
cavity
• GroES upon binding to GroEL serves as “lid”, which
encapsulates the volume inside the cavity
46. Complete their
cycle in 4 phases
Capture (T state)
ATP hydrolysis
(R’’ state)
Encapsulation
Substrate release
47.
48. A top-view of the GroES/GroEL bacterial
chaperone complex model
49. Chaperones andHuman Disease
It is clear that molecular
chaperones assist with the
folding of newly synthesized
proteins and correct protein
misfolding.
Recent studies now suggest that defects in
molecular chaperone/substrate interactions
may also play a substantial role in human
disease
50. For example
Mutations linked
to Alzheimer's
disease have
been shown to
disrupt the
expression of
chaperones in
the endoplasmic
reticulum
Several genes linked to
eye degeneration diseases
have recently been
identified as putative
molecular chaperones