Measuring cooperativity in the formation of a three-stranded β sheet (double hairpin)

✍ Scribed by F. Michael Hudson; Niels H. Andersen

• Publisher: Wiley (John Wiley & Sons)
• Year: 2006
• Tongue: English
• Weight: 199 KB
• Volume: 83
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20575

✦ Synopsis

Abstract

Recently validated chemical shift measures of hairpin structuring have been applied to a series of turn mutants of the Schenck–Gellman three‐strand β‐sheet model with the aim of measuring the entropic advantage associated with aligning an additional strand onto an existing hairpin versus aligning the same two strands in an initial hairpin formation. In a four‐state analysis (unfolded, 2 single hairpins, and the double hairpin fold in equilibrium) a cooperativity index can be defined as the factor by which the equilibrium constant for hairpin formation is improved when one strand is prestructured. This cooperativity index is 2.7 ± 0.7 for hairpin formation about a stable D‐Pro‐Gly turn locus and increases to 7.6 ± 1.2 for an Asn‐Gly turn locus. The latter corresponds to a cooperativity induced ΔΔ__G__ increment of 4.9 kJ/mol for the folding of a hairpin. Although larger than previous experimental measures of folding cooperativity in three‐stranded sheets, the magnitude of this effect (which is considerably less than the T__ΔΔ__S expectation for prestructuring three or more β‐strand residue sites) likely reflects the intrinsic preference of these designed sequences for extended conformations. If similar or larger effects apply to protein β‐sheet folding, it is not surprising that particularly favorable hairpin alignments serve as nucleation sites in protein folding pathways. © 2006 Wiley Periodicals, Inc. Biopolymers 83:424–433, 2006

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