2FPD

Sad structure determination: crystal structure of the intrinsic dimerization sh3 domain of the ib1 scaffold protein

Summary for 2FPD

• Entry DOI: 10.2210/pdb2fpd/pdb
• Related: 2FPE 2FPF
• Related PRD ID: PRD_900006
• Descriptor: C-jun-amino-terminal kinase interacting protein 1, alpha-D-glucopyranose-(1-1)-alpha-D-glucopyranose, SULFATE ION, ... (4 entities in total)
• Functional Keywords: src-homology 3 (sh3) domain, all beta structure, signaling protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 4
• Total formula weight: 30098.41

Authors

Kristensen, O.,Dar, I.,Gajhede, M. (deposition date: 2006-01-16, release date: 2006-02-28, Last modification date: 2020-07-29)

Primary citation

Kristensen, O.,Guenat, S.,Dar, I.,Allaman-Pillet, N.,Abderrahmani, A.,Ferdaoussi, M.,Roduit, R.,Maurer, F.,Beckmann, J.S.,Kastrup, J.S.,Gajhede, M.,Bonny, C.
A unique set of SH3-SH3 interactions controls IB1 homodimerization
Embo J., 25:785-797, 2006

PubMed Abstract: 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.

PubMed: 16456539
DOI: 10.1038/sj.emboj.7600982

Experimental method

X-RAY DIFFRACTION (2.05 Å)