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Title: Demonstration of long-range interactions in a PDZ domain by NMR, kinetics, and protein engineering.
Authors: Gianni, S
Walma, T
Arcovito, A
Calosci, N
Bellelli, A
Engström, A
Travaglini-Allocatelli, C
Brunori, M
Jemth, P
Vuister, GW
First Published: Dec-2006
Citation: STRUCTURE, 2006, 14 (12), pp. 1801-1809
Abstract: Understanding the basis of communication within protein domains is a major challenge in structural biology. We present structural and dynamical evidence for allosteric effects in a PDZ domain, PDZ2 from the tyrosine phosphatase PTP-BL, upon binding to a target peptide. The NMR structures of its free and peptide-bound states differ in the orientation of helix alpha2 with respect to the remainder of the molecule, concomitant with a readjustment of the hydrophobic core. Using an ultrafast mixing instrument, we detected a deviation from simple bimolecular kinetics for the association with peptide that is consistent with a rate-limiting conformational change in the protein (k(obs) approximately 7 x 10(3) s(-1)) and an induced-fit model. Furthermore, the binding kinetics of 15 mutants revealed that binding is regulated by long-range interactions, which can be correlated with the structural rearrangements resulting from peptide binding. The homologous protein PSD-95 PDZ3 did not display a similar ligand-induced conformational change.
DOI Link: 10.1016/j.str.2006.10.010
ISSN: 0969-2126
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

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