Molten globules, entropy-driven conformational change and protein folding

• Published in: Current opinion in structural biology Vol. 23; no. 1; pp. 4 - 10
• Main Authors: Baldwin, Robert L, Rose, George D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2013
• Subjects: Ligands; Protein Binding; Protein Conformation; Protein Folding; Protein Structure, Secondary; Proteins - chemistry; Thermodynamics
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2012.11.004

► Molten globules known to bind ligands include binding proteins and a designed enzyme. ► On ligand binding: binding proteins remain molten; designed enzyme folds. ► Conformational entropy of side chains found by NMR line broadening. ► Changes in entropy upon effector binding, though far from site, help to drive binding. The exquisite side chain close-packing in the protein core and at binding interfaces has prompted a conviction that packing selectivity is the primary mechanism for molecular recognition in folding and/or binding reactions. Contrary to this view, molten globule proteins can adopt native topology and bind targets tightly and specifically in the absence of side chain close-packing. The molten globule is a highly dynamic form with native-like secondary structure and a loose protein core that admits solvent. The related (but still controversial) dry molten globule is an expanded form of the native protein with largely intact topology but a tighter protein core that excludes solvent. Neither form retains side chain close-packing, and therefore both structure and function must result from other factors, assuming that the reality of the dry molten globule is accepted. This simplifying realization calls for a re-evaluation of established models.