1vj6
PDZ2 from PTP-BL in complex with the C-terminal ligand from the APC protein
Structural highlights
FunctionPTN13_MOUSE Tyrosine phosphatase which regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUnderstanding 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. Demonstration of long-range interactions in a PDZ domain by NMR, kinetics, and protein engineering.,Gianni S, Walma T, Arcovito A, Calosci N, Bellelli A, Engstrom A, Travaglini-Allocatelli C, Brunori M, Jemth P, Vuister GW Structure. 2006 Dec;14(12):1801-9. PMID:17161370[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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