1OO4

P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase complexed to a peptide derived from PDGFr

Summary for 1OO4

• Entry DOI: 10.2210/pdb1oo4/pdb
• Related: 1OO3
• Descriptor: Phosphatidylinositol 3-kinase regulatory alpha subunit, 8-mer peptide from PDGFr (2 entities in total)
• Functional Keywords: src homology 2 domain p85 regulatory subunit mutant, pdgfr complex, protein binding
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 2
• Total formula weight: 13863.41

Authors

Guenther, U.L.,Weyrauch, B.,Schaffhausen, B. (deposition date: 2003-03-03, release date: 2003-03-25, Last modification date: 2024-10-23)

Primary citation

Guenther, U.L.,Weyrauch, B.,Zhang, X.,Schaffhausen, B.
Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity
Biochemistry, 42:11120-11127, 2003

PubMed Abstract: Understanding the specificity of Src homology 2 (SH2) domains is important because of their critical role in cell signaling. Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K). The P395S mutant exhibits a specificity for phosphopeptide binding different from that of the wild-type SH2. The P395S mutant has an increased affinity for the platelet-derived growth factor receptor (PDGFr) compared to polyomavirus middle T antigen (MT). Solution structures of the P395S mutant of the p85 N-SH2 alone and complexed to a PDGFr phosphopeptide were determined to explain the change in specificity. Chemical shift perturbations caused by different peptides were compared for mutant and wild-type structures. The results show that the single P395S mutation has broad effects on the structure. Furthermore, they provide a rationale for the observed changes in binding preference.

PubMed: 14503862
DOI: 10.1021/bi034353x

Experimental method

SOLUTION NMR