Universal Nature of Collapsibility in the Context of Protein Folding and Evolution. Issue 8 (August 2019)

• Record Type: Journal Article
• Authors: Thirumalai, D.; Samanta, Himadri S.; Maity, Hiranmay; Reddy, Govardhan
• Is Part Of: Trends in biochemical sciences. Volume 44:Issue 8(2019)
• Page Start: 675
• Page End: 687
• Publication Date: 2019-08
• Subjects: Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2019.04.003
• Languages: English
• ISSNs: 0968-0004

Abstract

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 Förster 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 β -sheets are more collapsible than α -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. Highlights: Collapsibility of single domain proteins is universal. Sizes of unfolded states of globular proteins decrease as denaturant concentration is decreased. Proteins rich in β -sheets have higher propensity to collapse than those rich in α -helices. Collapsibility could explain the origin of multidomain proteins. Evolution of natural sequences could be due to the need to be collapsible.