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. 2018 May 20:47:19-39.
doi: 10.1146/annurev-biophys-070317-032838. Epub 2018 Jan 18.

Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and Solvent Interactions

Alex S Holehouse  1 , Rohit V Pappu  1
Affiliations

Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and Solvent Interactions

Alex S Holehouse et al. Annu Rev Biophys. .

Abstract

Proteins can collapse into compact globules or form expanded, solvent-accessible, coil-like conformations. Additionally, they can fold into well-defined three-dimensional structures or remain partially or entirely disordered. Recent discoveries have shown that the tendency for proteins to collapse or remain expanded is not intrinsically coupled to their ability to fold. These observations suggest that proteins do not have to form compact globules in aqueous solutions. They can be intrinsically disordered, collapsed, or expanded, and even form well-folded, elongated structures. This ability to decouple collapse from folding is determined by the sequence details of proteins. In this review, we highlight insights gleaned from studies over the past decade. Using a polymer physics framework, we explain how the interplay among sidechains, backbone units, and solvent determines the driving forces for collapsed versus expanded states in aqueous solvents.

Keywords: collapse; intrinsically disordered proteins; polymer physics; solvent quality; unfolded states.

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Figures

Figure 1
Figure 1
(a) The coil-to-globule transition curve for a 100-residue homopolymer as a function of monomer–monomer interaction strength with representative ensemble snapshots. The sigmoidal shape is characteristic of a cooperative transition, as observed for complex heteropolymers and simple homopolymers alike. (b) The molecular structure of a polypeptide. A single backbone peptide unit is highlighted at the top; this structure repeats down the chain. Various sidechains are circled in red.
Figure 2
Figure 2
Conformational classifications of polypeptides based on the two-dimensional space of conformational heterogeneity and global dimensions. Examples for each are the crystal structure of SasG (top left), the conformational ensemble of Ash1 (top right), the conformational ensemble for polyglutamine (bottom right), and the crystal structure of lysozyme (bottom left) (PDB: 1IEE) (51, 89, 140). The decoupling of global dimensions and conformational heterogeneity is formally addressed in Reference .
Figure 3
Figure 3
(a) Scaling behavior for folded proteins based on ~2,400 nonredundant structures taken from PDBSELECT25 (49). While the radius of gyration shows reasonable agreement with vapp≈0.33, the end-to-end distance shows a poor correlation (inset). (b) Scaling behavior for chemically denatured proteins based on data from Reference . The unfolded state under strongly denaturing conditions is well described by a self-avoiding random chain (vapp≈0.59).
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