1NZL

Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYEpYIPI

Summary for 1NZL

• Entry DOI: 10.2210/pdb1nzl/pdb
• Related: 1IS0 1KC2
• Descriptor: Tyrosine-protein kinase transforming protein SRC, Doubly phosphorylated peptide ligand (PQpYEpYIPI), CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: sh2 domain, phosphotyrosine, transferase
• Biological source: Rous sarcoma virus (strain Schmidt-Ruppin)
• Total number of polymer chains: 3
• Total formula weight: 25089.86

Authors

Lubman, O.Y.,Waksman, G. (deposition date: 2003-02-18, release date: 2003-04-22, Last modification date: 2024-10-16)

Primary citation

Lubman, O.Y.,Waksman, G.
Structural and Thermodynamic Basis for the Interaction of the Src SH2 domain with the Activated form of the PDGF beta-receptor
J.Mol.Biol., 328:655-668, 2003

PubMed Abstract: Recruitment of the Src kinase to the activated form of the platelet-derived growth factor (PDGF) receptor involves recognition of a unique sequence motif in the juxtamembrane region of the receptor by the Src homology 2 (SH2) domain of the enzyme. This motif contains two phosphotyrosine residues separated by one residue (sequence pYIpYV where pY indicates a phosphotyrosine). Here, we provide the thermodynamic and structural basis for the binding of this motif by the Src SH2 domain. We show that the second phosphorylation event increases the free energy window for specific interaction and that the physiological target is exquisitely designed for the task of recruiting specifically an SH2 domain which otherwise demonstrates very little intrinsic ability to discriminate sequences C-terminal to the first phosphorylation event. Surprisingly, we show that water plays a role in the recognition process.

PubMed: 12706723
DOI: 10.1016/S0022-2836(03)00344-9

Experimental method

X-RAY DIFFRACTION (1.9 Å)