Structural highlights
Disease
IGBP1_HUMAN Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia. Defects in IGBP1 are the cause of mental retardation syndromic X-linked type 28 (MRXS28) [MIM:300472; also known as agenesis of the corpus callosum with mental retardation, ocular coloboma and micrognathia. A syndrome that is characterized by coloboma of the iris and optic nerve, severe retrognathia, intellectual deficit, and agenesis of the corpus callosum.[1]
Function
IGBP1_HUMAN Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of PP2A, PP4 and PP6 phosphatases catalytic subunits by protecting them from degradative polyubiquitination until they associate with regulatory subunits.[2]
Publication Abstract from PubMed
The catalytic subunit of protein phosphatase 2A (PP2Ac) is stabilized in a latent form by alpha4, a regulatory protein essential for cell survival and biogenesis of all PP2A complexes. Here we report the structure of alpha4 bound to the N-terminal fragment of PP2Ac. This structure suggests that alpha4 binding to the full-length PP2Ac requires local unfolding near the active site, which perturbs the scaffold subunit binding site at the opposite surface via allosteric relay. These changes stabilize an inactive conformation of PP2Ac and convert oligomeric PP2A complexes to the alpha4 complex upon perturbation of the active site. The PP2Ac-alpha4 interface is essential for cell survival and sterically hinders a PP2A ubiquitination site, important for the stability of cellular PP2Ac. Our results show that alpha4 is a scavenger chaperone that binds to and stabilizes partially folded PP2Ac for stable latency, and reveal a mechanism by which alpha4 regulates cell survival, and biogenesis and surveillance of PP2A holoenzymes.
Structural basis of protein phosphatase 2A stable latency.,Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y Nat Commun. 2013;4:1699. doi: 10.1038/ncomms2663. PMID:23591866[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Graham JM Jr, Wheeler P, Tackels-Horne D, Lin AE, Hall BD, May M, Short KM, Schwartz CE, Cox TC. A new X-linked syndrome with agenesis of the corpus callosum, mental retardation, coloboma, micrognathia, and a mutation in the Alpha 4 gene at Xq13. Am J Med Genet A. 2003 Nov 15;123A(1):37-44. PMID:14556245 doi:10.1002/ajmg.a.20504
- ↑ Kong M, Ditsworth D, Lindsten T, Thompson CB. Alpha4 is an essential regulator of PP2A phosphatase activity. Mol Cell. 2009 Oct 9;36(1):51-60. PMID:19818709 doi:S1097-2765(09)00685-6
- ↑ Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y. Structural basis of protein phosphatase 2A stable latency. Nat Commun. 2013;4:1699. doi: 10.1038/ncomms2663. PMID:23591866 doi:10.1038/ncomms2663
