Universal Nature of Collapsibility in the Context of Protein Folding and Evolution

Thirumalai, D. and Samanta, Himadri S and Maity, Hiranmay and Reddy, Govardhan (2019) Universal Nature of Collapsibility in the Context of Protein Folding and Evolution. In: TRENDS IN BIOCHEMICAL SCIENCES, 44 (8). pp. 675-687.

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Abstract

Theory and simulations predicted that the sizes of the unfolded states of globular proteins should decrease as the denaturant concentration is reduced from a high to a low value. However, small angle X-ray scattering (SAXS) data were used to assert the opposite, while interpretation of single molecule Forster resonance energy transfer experiments (FRET) supported the theoretical predictions. The disagreement between the two experiments is the SAXS-FRET controversy. By harnessing recent advances in SAXS and FRET experiments and setting these findings in the context of a general theory and simulations, which do not rely on experimental data, we establish that compaction of unfolded states under native conditions is universal. The theory also predicts that proteins rich in beta-sheets are more collapsible than alpha-helical proteins. Because the extent of compaction is small, experiments have to be accurate and their interpretations should be as model-free as possible. Theory also suggests that collapsibility itself could be a physical restriction on the evolution of foldable sequences, and also provides a physical basis for the origin of multidomain proteins.

Item Type:	Journal Article
Publication:	TRENDS IN BIOCHEMICAL SCIENCES
Publisher:	ELSEVIER SCIENCE LONDON
Additional Information:	copyright for this article belongs to Cell Press.
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	20 Aug 2019 10:56
Last Modified:	03 Sep 2019 10:09
URI:	http://eprints.iisc.ac.in/id/eprint/63293

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