1RPY

CRYSTAL STRUCTURE OF THE DIMERIC SH2 DOMAIN OF APS

Summary for 1RPY

• Entry DOI: 10.2210/pdb1rpy/pdb
• Descriptor: adaptor protein APS, SULFATE ION (3 entities in total)
• Functional Keywords: adapter protein, sh2 domain, signaling protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: Q9Z200
• Total number of polymer chains: 2
• Total formula weight: 26069.27

Authors

Hu, J.,Liu, J.,Ghirlando, R.,Saltiel, A.R.,Hubbard, S.R. (deposition date: 2003-12-03, release date: 2003-12-23, Last modification date: 2024-10-30)

Primary citation

Hu, J.,Liu, J.,Ghirlando, R.,Saltiel, A.R.,Hubbard, S.R.
Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor.
Mol.Cell, 12:1379-1389, 2003

PubMed Abstract: The adaptor protein APS is a substrate of the insulin receptor and couples receptor activation with phosphorylation of Cbl to facilitate glucose uptake. The interaction with the activated insulin receptor is mediated by the Src homology 2 (SH2) domain of APS. Here, we present the crystal structure of the APS SH2 domain in complex with the phosphorylated tyrosine kinase domain of the insulin receptor. The structure reveals a novel dimeric configuration of the APS SH2 domain, wherein the C-terminal half of each protomer is structurally divergent from conventional, monomeric SH2 domains. The APS SH2 dimer engages two kinase molecules, with pTyr-1158 of the kinase activation loop bound in the canonical phosphotyrosine binding pocket of the SH2 domain and a second phosphotyrosine, pTyr-1162, coordinated by two lysine residues in beta strand D. This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor.

PubMed: 14690593
DOI: 10.1016/S1097-2765(03)00487-8

Experimental method

X-RAY DIFFRACTION (2.3 Å)