Hydrophobic core fluidity of homologous protein domains: relation of side-chain dynamics to core composition and packing.

Abstract:

:The side-chain dynamics of methyl groups in two structurally related proteins from the fibronectin type III (fnIII) superfamily, the third fnIII domain from human tenascin (TNfn3) and the tenth fnIII domain from human fibronectin (FNfn10), have been studied by NMR spectroscopy. Side-chain order parameters reveal that the hydrophobic cores of the two proteins have substantially different mobilities. The core of TNfn3 is very dynamic, with exceptionally low order parameters for the most deeply buried residues, while that of FNfn10 is more like those of other proteins which have been studied with this technique, having a relatively rigid core with uniformly distributed dynamics. The unusually dynamic core of TNfn3 appears to be related to its amino acid composition, which makes it more fluid-like. A further explanation for the mobility of the TNfn3 core may be found in the negative correlation between the order parameter and excess packing volume, which shows that the core of TNfn3 is less densely packed and consequently has lower methyl order parameters for its buried residues. Rotameric transitions, presumably facilitated by the lower packing density, appear to make an important contribution to lowering the order parameters, and have been probed by measuring three-bond scalar couplings. Overall, although backbone dynamics is generally similar for proteins with the same topology on a fast time scale (picoseconds to nanoseconds), this study shows that a single fold can accommodate a wide variation in the dynamic properties of its core.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Best RB,Rutherford TJ,Freund SM,Clarke J

doi

10.1021/bi035658e

subject

Has Abstract

pub_date

2004-02-10 00:00:00

pages

1145-55

issue

5

eissn

0006-2960

issn

1520-4995

journal_volume

43

pub_type

杂志文章