3ued
Crystal structure of human Survivin bound to histone H3 phosphorylated on threonine-3 (C2 space group).
Structural highlights
FunctionBIRC5_HUMAN Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedSurvivin, a subunit of the Chromosome Passenger Complex, binds the N-terminal tail of histone H3, which is phosphorylated on T3 by Haspin kinase, and localizes the complex to the inner centromeres. We used X-ray crystallography to determine the residues of Survivin that are important in binding phosphomodified histone H3. Mutation of amino acids that interact with the histone N-terminus lowered in vitro tail binding affinity and reduced CPC recruitment to the inner centromere in cells, validating our solved structures. Phylogenetic analysis shows that non-mammalian vertebrates have two Survivin paralogs, which we name Class A and B. A distinguishing feature of these paralogs is H to R change in an amino acid that interacts with the histone T3 phosphate. The binding to histone tails of the human Class A paralog, which has a histidine at this position, is sensitive to changes around physiological pH, while Xenopus Survivin Class B is less so. Our data demonstrate that Survivin paralogs have different characteristics of phosphospecific binding to threonine-3 of histone H3, providing new insight into the biology of the inner centromere. Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogs at inner centromeres.,Niedzialkowska E, Wang F, Porebski PJ, Minor W, Higgins JM, Stukenberg PT Mol Biol Cell. 2012 Feb 22. PMID:22357620[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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