characterization of 14-3-3 proteins from cryptosporidium parvum描述14-3-3小球隐孢子虫的蛋白质.pdfVIP

Characterization of 14-3-3 Proteins from Cryptosporidium parvum 1 1 1 1 1 1 Stephen J. Brokx , Amy K. Wernimont , Aiping Dong , Gregory A. Wasney , Yu-Hui Lin , Jocelyne Lew , 1 2 1 Masoud Vedadi , Wen Hwa Lee , Raymond Hui * 1 Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada, 2 Structural Genomics Consortium, University of Oxford, Headington, Oxford, United Kingdom Abstract The parasite Cryptosporidium parvum has three 14-3-3 proteins: Cp14e, Cp14a and Cp14b, with only Cp14e similar to human 14-3-3 proteins in sequence, peptide-binding properties and structure. Structurally, Cp14a features the classical 14-3-3 dimer but with a uniquely wide pocket and a disoriented RRY triad potentially incapable of binding phosphopeptides. The Cp14b protein deviates from the norm significantly: (i) In one subunit, the phosphorylated C-terminal tail is bound in the binding groove like a phosphopeptide. This supports our binding study indicating this protein was stabilized by a peptide mimicking its last six residues. (ii) The other subunit has eight helices instead of nine, with aA and aB forming a single helix and occluding the peptide-binding cleft. (iii) The protein forms a degenerate dimer with the two binding grooves divided and facing opposite directions. These features conspire to block and disrupt the bicameral substrate-binding pocket, suggesting a possible tripartite auto-regulation mechanism that has not been observed previously. Enhanced version: This article can also be viewed as an enhanced version (/enhanced/pone.0014827/) in which the text of the article is integrated with interactive 3D repr