4TZI

Structure of unliganded Lyn SH2 domain

Summary for 4TZI

• Entry DOI: 10.2210/pdb4tzi/pdb
• Descriptor: Tyrosine-protein kinase Lyn (2 entities in total)
• Functional Keywords: sh2 domain, transferase
• Biological source: Mus musculus (Mouse)
• Cellular location: Cell membrane : P25911
• Total number of polymer chains: 2
• Total formula weight: 26398.00

Authors

Wybenga-Groot, L.E. (deposition date: 2014-07-10, release date: 2015-01-21, Last modification date: 2023-09-27)

Primary citation

Jin, L.L.,Wybenga-Groot, L.E.,Tong, J.,Taylor, P.,Minden, M.D.,Trudel, S.,McGlade, C.J.,Moran, M.F.
Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity.
Mol.Cell Proteomics, 14:695-706, 2015

PubMed Abstract: Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases.

PubMed: 25587033
DOI: 10.1074/mcp.M114.044404

Experimental method

X-RAY DIFFRACTION (2.1 Å)