2fpd
From Proteopedia
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'''Sad structure determination: crystal structure of the intrinsic dimerization sh3 domain of the ib1 scaffold protein''' | '''Sad structure determination: crystal structure of the intrinsic dimerization sh3 domain of the ib1 scaffold protein''' | ||
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[[Category: Gajhede, M.]] | [[Category: Gajhede, M.]] | ||
[[Category: Kristensen, O.]] | [[Category: Kristensen, O.]] | ||
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Revision as of 01:10, 4 May 2008
Sad structure determination: crystal structure of the intrinsic dimerization sh3 domain of the ib1 scaffold protein
Overview
Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components and secretion. IB1 has been shown to homodimerize, but neither the molecular mechanisms nor the function of dimerization have yet been characterized. Here, we show that IB1 homodimerizes through a novel and unique set of Src homology 3 (SH3)-SH3 interactions. X-ray crystallography studies show that the dimer interface covers a region usually engaged in PxxP-mediated ligand recognition, even though the IB1 SH3 domain lacks this motif. The highly stable IB1 homodimer can be significantly destabilized in vitro by three individual point mutations directed against key residues involved in dimerization. Each mutation reduces IB1-dependent basal JNK activity in 293T cells. Impaired dimerization also results in a reduction in glucose transporter type 2 expression and in glucose-dependent insulin secretion in pancreatic beta-cells. Taken together, these results indicate that IB1 homodimerization through its SH3 domain has pleiotropic effects including regulation of the insulin secretion process.
About this Structure
2FPD is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
A unique set of SH3-SH3 interactions controls IB1 homodimerization., Kristensen O, Guenat S, Dar I, Allaman-Pillet N, Abderrahmani A, Ferdaoussi M, Roduit R, Maurer F, Beckmann JS, Kastrup JS, Gajhede M, Bonny C, EMBO J. 2006 Feb 22;25(4):785-97. Epub 2006 Feb 2. PMID:16456539 Page seeded by OCA on Sun May 4 04:10:00 2008
