Pharmacological chaperones: a new twist on receptor folding (original) (raw)
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Intramolecular chaperones: polypeptide extensions that modulate protein folding
Seminars in Cell & Developmental Biology, 2000
Several prokaryotic and eukaryotic proteins are synthesized as precursors in the form of pre-pro-proteins. While the pre-regions function as signal peptides that are involved in transport, the propeptides can often catalyze correct folding of their associated proteins. Such propeptides have been termed intramolecular chaperones. In cases where propeptides may not directly catalyze the folding reaction, it appears that they can facilitate processes such as structural organization and oligomerization, localization, sorting and modulation of enzymatic activity and stability of proteins. Based on the available literature it appears that propeptides may actually function as ' post-translational modulators' of protein structure and function. Propeptides can be classified into two broad categories: Class I propeptides that function as intramolecular chaperones and directly catalyze the folding reaction; and Class II propeptides that are not directly involved in folding.
Protein Folding Assisted by Chaperones
Protein & Peptide Letters, 2005
Molecular chaperones are one of the most important cell defense mechanisms against protein aggregation and misfolding. These specialized proteins bind non-native states of other proteins and assist them in reaching a correctly folded and functional conformation. Chaperones also participate in protein translocation by membranes, in the stabilization of unstable protein conformers and regulatory factors, in the delivery of substrates for proteolysis and in the recovery of proteins from aggregates.
Protein quality control: chaperones culling corrupt conformations
Nature Cell Biology, 2005
Achieving the correct balance between folding and degradation of misfolded proteins is critical for cell viability. The importance of defining the mechanisms and factors that mediate cytoplasmic quality control is underscored by the growing list of diseases associated with protein misfolding and aggregation. Molecular chaperones assist protein folding and also facilitate degradation of misfolded polypeptides by the ubiquitin–proteasome system. Here
International Journal of Research Studies in Medical and Health Sciences, 2021
Introduction: The endoplasmic reticulum is an organelle that functions as a place for protein folding. The process of folding protein involves several components including: chaperones, calcium, and several related enzymes. Capheron molecules function to help the protein folding process, slow down the folding speed of proteins so as to prevent protein aggregation. The supervisor also has a role to maintain calcium homeostasis in the ER, where homeostasis can be achieved in the RE lumen calcium concentration of about 400 μM due to the role of the companion interaction with the SERCA receptor and IP3 receptor. Calcium itself plays a direct role in the protein folding process by modulating chaperon bonds with carbohydrates in N-glycoproteins so that chaperons can function to help protein folding. Discussion: Quality Control is also carried out by calnexin and calreticulin, which play a role in the correct folding of proteins and also recognize protein misfolding which then tries to fold it back. This role is supported by the presence of calcium in the RE lumen. The misfolding protein will increase calreticulin expression, then calreticulin through a certain mechanism influences the SERCA receptor so that there is an increase in the concentration of calcium in the RE lumen. Calcium then helps calreticulin in carrying out its function by modulating the interaction between calreticulin and carbohydrates so that refolding can occur. Proteins that have been completely molded are then removed from the ER, on the other hand, if they cannot be refolded, they will enter the ERAD mechanism and then be brought to the proteosome and degraded. Conclusion: Proteins are subjected to quality control checks and any found to be misformed or folded incorrectly will be rejected. This rejection hail is stored in the lumen or sent for recycling for its eventual breakdown into amino acids. There are many disease related to protein foldings and quality control in RE. A type of emphysema (lung problem) is caused by the RE quality control department constantly rejecting the protein incorrectly folded. The protein needed was never exported from the crude RE. Quality control plays a role in cystic fibrosis. A form of cystic fibrosis is caused by a single missing amino acid, phenylanaline, in a specific position in the protein construction. Proteins can work well without amino acids but these services must be precisely provided by quality control for speck of error and resist storage of protein in the crude RE lumen.
The role of molecular chaperones in protein folding
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1995
Folding of newly synthesized polypeptides in the crowded cellular environment requires the assistance of so-called molecular chaperone proteins. Chaperones of the Hsp70 class and their partner proteins interact with nascent polypeptide chains on ribosomes and prevent their premature (mis)folding at least until a domain capable of forming a stable structure is synthesized. For many proteins, completion of folding requires the subsequent interaction with one of the large oligomeric ring-shaped proteins of the chaperonin family, which is composed of the GroEL-like proteins in eubacteria, mitochondria, and chloroplasts, and the TRiC family in eukaryotic cytosol and archaea. These proteins bind partially folded polypeptide in their central cavity and promote folding by ATP-dependent cycles of release and rebinding. In these reactions, molecular chaperones interact predominantly with the hydrophobic surfaces exposed by nonnative polypeptides, thereby preventing incorrect folding and aggre...
Role of Molecular Chaperones in Protein Folding
Current and Emerging Principles and Therapies, 2010
Folding of newly synthesized polypeptides in the crowded cellular environment requires the assistance of so-called molecular chaperone proteins. Chaperones of the Hsp7O class and their partner proteins interact with nascent polypeptide chains on ribosomes and prevent their premature (mis)folding at least until a domain capable of forming a stable structure issynthesized. For many proteins, completion of folding requires the subsequeiit interaction with one of the large oligomeric ring-shaped proteins of the chaperonin family, which is composed of tile GroEL-like proteins in eubacteria, mitochondria, and chioroplasts, and the TRiC family in eukaryotic cytosol and archaea. These proteins bind partially folded polypeptide in their central cavity and promote folding by ATP-dependent cycles of release and rebinding. In these reactions, molecular chaperones interact predominantly with the hydrophobic surfaces exposed by nonnative polypeptides, thereby preventing incorrect folding and aggregatiou.-Hendrick, J. P., Harti, F.-U. The role of molecular chaperones in protein folding.
FEBS Journal, 2008
Protein aggregation is the result of the mutual association of partially folded intermediate states of a protein, most likely via predominately hydrophobic interactions. Protein aggregation can proceed via disordered or ordered mechanisms: which mechanism predominates is thought to be determined by a number of factors, including the rate of unfolding, the amino acid sequence of the protein, the experimental conditions and the nature of the intermediate state(s) that form . Disordered aggregation results in amorphous aggregates of protein, whilst ordered aggregation produces amyloid fibrils, long threadlike protein structures that are rich in b-sheet and resistant to proteolytic degradation. Protein misfolding, and in particular amyloid fibril formation, is associated with a range of diseases, including Alzheimer's, Parkinson's and Creutzfeldt-Jakob diseases, type II diabetes and possibly cataracts . Protein aggregation is also responsible for inclusion body formation, and therefore the ability to prevent it would be of enormous benefit in recombinant protein production, avoiding the need for resolubilization of the aggregated and precipitated protein. Thus, studies aimed at preventing protein aggregation are of interest due to both their biomedical and biotechnological applications.