Structure of a human p110alpha/p85alpha complex (2rd0)
(see also Phosphoinositide 3-Kinases)
Publication Abstract from PubMed
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.
The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations., Huang CH, Mandelker D, Schmidt-Kittler O, Samuels Y, Velculescu VE, Kinzler KW, Vogelstein B, Gabelli SB, Amzel LM, Science. 2007 Dec 14;318(5857):1744-8. PMID:18079394
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Disease
Known disease associated with this structure: Breast cancer, somatic OMIM:[171834], Colorectal cancer, somatic OMIM:[171834], Gastric cancer, somatic OMIM:[171834], Hepatocellular carcinoma, somatic OMIM:[171834], Nonsmall cell lung cancer, somatic OMIM:[171834], Ovarian cancer, somatic OMIM:[171834]
About this Structure
2RD0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Figures From The Publication
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- (Figure 2D requires a model containing the nSH2 domain, not present in the published model 2rd0.)
- Re: Figure 3 -- :
iSH2 (chain B),
Negative,
Positive.
Asp, Glu sidechain oxygens,
Lys, Arg terminal sidechain nitrogens.
No sidechains lack coordinates in this model.
The following residues are missing in the model (lack coordinates):
- Chain A: 1-7, 307-324, 415-423, 506-527, 941-950. The last modeled residue is 1050.
- Chain B: 1-441, 510-520, 584-592. The last modeled residue is 600.
Created with the participation of Eric Martz, Eran Hodis, Jaime Prilusky.
