2HDV

Crystal structure of the Src Homology-2 domain of the adapter protein SH2-B

Summary for 2HDV

• Entry DOI: 10.2210/pdb2hdv/pdb
• Descriptor: SH2-B PH domain containing signaling mediator 1 gamma isoform (2 entities in total)
• Functional Keywords: sh2, adapter protein, signaling protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 24551.98

Authors

Hu, J.,Hubbard, S.R. (deposition date: 2006-06-20, release date: 2006-08-08, Last modification date: 2023-08-30)

Primary citation

Hu, J.,Hubbard, S.R.
Structural Basis for Phosphotyrosine Recognition by the Src Homology-2 Domains of the Adapter Proteins SH2-B and APS.
J.Mol.Biol., 361:69-79, 2006

PubMed Abstract: SH2-B, APS, and Lnk constitute a family of adapter proteins that modulate signaling by protein tyrosine kinases. These adapters contain an N-terminal dimerization region, a pleckstrin homology domain, and a C-terminal Src homology-2 (SH2) domain. SH2-B is recruited via its SH2 domain to various protein tyrosine kinases, including Janus kinase-2 (Jak2) and the insulin receptor. Here, we present the crystal structure at 2.35 A resolution of the SH2 domain of SH2-B in complex with a phosphopeptide representing the SH2-B recruitment site in Jak2 (pTyr813). The structure reveals a canonical SH2 domain-phosphopeptide binding mode, but with specific recognition of a glutamate at the +1 position relative to phosphotyrosine, in addition to recognition of a hydrophobic residue at the +3 position. Biochemical studies of SH2-B and APS demonstrate that, although the SH2 domains of these two adapter proteins share 79% sequence identity, the SH2-B SH2 domain binds preferentially to Jak2, whereas the APS SH2 domain has higher affinity for the insulin receptor. This differential specificity is attributable to the difference in the oligomeric states of the two SH2 domains: monomeric for SH2-B and dimeric for APS.

PubMed: 16824542
DOI: 10.1016/j.jmb.2006.05.070

Experimental method

X-RAY DIFFRACTION (2 Å)