2RD0

Structure of a human p110alpha/p85alpha complex

2RD0 の概要

• エントリーDOI: 10.2210/pdb2rd0/pdb
• 分子名称: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, Phosphatidylinositol 3-kinase regulatory subunit alpha (2 entities in total)
• 機能のキーワード: disease mutation, kinase, oncogene, transferase, host-virus interaction, phosphorylation, sh2 domain, sh3 domain, transferase-oncoprotein complex, transferase/oncoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 161489.54

構造登録者

Huang, C.,Gabelli, S.B.,Amzel, L.M. (登録日: 2007-09-20, 公開日: 2007-12-25, 最終更新日: 2024-02-21)

主引用文献

Huang, C.H.,Mandelker, D.,Schmidt-Kittler, O.,Samuels, Y.,Velculescu, V.E.,Kinzler, K.W.,Vogelstein, B.,Gabelli, S.B.,Amzel, L.M.
The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations.
Science, 318:1744-1748, 2007

PubMed Abstract: PIK3CA, one of the two most frequently mutated oncogenes in human tumors, codes for p110alpha, the catalytic subunit of a phosphatidylinositol 3-kinase, isoform alpha (PI3Kalpha, p110alpha/p85). Here, we report a 3.0 angstrom resolution structure of a complex between p110alpha and a polypeptide containing the p110alpha-binding domains of p85alpha, a protein required for its enzymatic activity. The structure shows that many of the mutations occur at residues lying at the interfaces between p110alpha and p85alpha or between the kinase domain of p110alpha and other domains within the catalytic subunit. Disruptions of these interactions are likely to affect the regulation of kinase activity by p85 or the catalytic activity of the enzyme, respectively. In addition to providing new insights about the structure of PI3Kalpha, these results suggest specific mechanisms for the effect of oncogenic mutations in p110alpha and p85alpha.

PubMed: 18079394
DOI: 10.1126/science.1150799

実験手法

X-RAY DIFFRACTION (3.05 Å)