2fpf

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[[Image:2fpf.gif|left|200px]]
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{{STRUCTURE_2fpf| PDB=2fpf | SCENE= }}
{{STRUCTURE_2fpf| PDB=2fpf | SCENE= }}
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'''Crystal structure of the ib1 sh3 dimer at low resolution'''
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===Crystal structure of the ib1 sh3 dimer at low resolution===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_16456539}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 16456539 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16456539}}
==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/16456539 16456539]
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:[http://www.ncbi.nlm.nih.gov/pubmed/16456539 16456539]
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A cytoplasmic inhibitor of the JNK signal transduction pathway., Dickens M, Rogers JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL, Davis RJ, Science. 1997 Aug 1;277(5326):693-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9235893 9235893]
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IB1, a JIP-1-related nuclear protein present in insulin-secreting cells., Bonny C, Nicod P, Waeber G, J Biol Chem. 1998 Jan 23;273(4):1843-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9442013 9442013]
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Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation regulates JNK module dynamics and activation., Nihalani D, Wong HN, Holzman LB, J Biol Chem. 2003 Aug 1;278(31):28694-702. Epub 2003 May 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12756254 12756254]
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The JIP group of mitogen-activated protein kinase scaffold proteins., Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ, Mol Cell Biol. 1999 Oct;19(10):7245-54. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10490659 10490659]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Mitogen-activated protein kinase 8-interacting protein 1]]
[[Category: Mitogen-activated protein kinase 8-interacting protein 1]]
[[Category: Scaffold protein 1]]
[[Category: Scaffold protein 1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:10:00 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:52:16 2008''

Revision as of 12:52, 29 July 2008

Image:2fpf.png

Template:STRUCTURE 2fpf

Crystal structure of the ib1 sh3 dimer at low resolution

Template:ABSTRACT PUBMED 16456539

About this Structure

2FPF 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

A cytoplasmic inhibitor of the JNK signal transduction pathway., Dickens M, Rogers JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL, Davis RJ, Science. 1997 Aug 1;277(5326):693-6. PMID:9235893

IB1, a JIP-1-related nuclear protein present in insulin-secreting cells., Bonny C, Nicod P, Waeber G, J Biol Chem. 1998 Jan 23;273(4):1843-6. PMID:9442013

Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation regulates JNK module dynamics and activation., Nihalani D, Wong HN, Holzman LB, J Biol Chem. 2003 Aug 1;278(31):28694-702. Epub 2003 May 19. PMID:12756254

The JIP group of mitogen-activated protein kinase scaffold proteins., Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ, Mol Cell Biol. 1999 Oct;19(10):7245-54. PMID:10490659

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