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Protein folding and the order/disorder paradox
Prakash Kulkarni1, Krithika Rajagopalan, David Yeater
1Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. pkulkar4@jhmi.edu
Journal of Cellular Biochemistry
|March 30, 2011
Summary
Intrinsically disordered proteins (IDPs) evade cellular quality control by coupling folding and binding, unlike misfolded globular proteins. This disorder-to-order transition helps them escape degradation pathways.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- Most proteins fold into specific 3D structures with molecular chaperone assistance.
- Misfolded proteins are targeted for degradation by cellular quality control (QC) mechanisms.
- A significant portion of the proteome consists of Intrinsically Disordered Proteins (IDPs) lacking rigid structures.
Purpose of the Study:
- To investigate the paradox of how IDPs evade cellular QC.
- To understand the mechanisms by which IDPs escape degradation.
- To explore the implications for protein folding and disease biology.
Main Methods:
- Comparative analysis of protein folding pathways.
- Examination of cellular quality control surveillance.
- Postulation of IDP evasion mechanisms based on structural dynamics.
Main Results:
- IDPs exist as dynamic ensembles, not rigid structures.
- IDPs share structural similarities with states seen during globular protein folding.
- IDPs evade degradation by the cellular QC system.
Conclusions:
- IDPs likely escape QC by utilizing their intrinsic disorder and disorder-to-order transitions upon target binding.
- Understanding IDP evasion mechanisms is crucial for comprehending protein folding and diseases linked to protein misfolding, such as neurodegenerative disorders and cancer.
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