Structural representative of the protein family PF14466 has a new fold and establishes links with the C2 and PLAT domains from the widely distant Pfams PF00168 and PF01477

Authors

  • Pedro Serrano,

    1. Joint Center for Structural Genomics, La Jolla, California
    2. Department of Integrative Structural and Computational Biology and
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  • Michael Geralt,

    1. Joint Center for Structural Genomics, La Jolla, California
    2. Department of Integrative Structural and Computational Biology and
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  • Biswaranjan Mohanty,

    1. Joint Center for Structural Genomics, La Jolla, California
    2. Department of Integrative Structural and Computational Biology and
    3. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California
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  • Kurt Wüthrich

    Corresponding author
    1. Department of Integrative Structural and Computational Biology and
    2. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California
    • Joint Center for Structural Genomics, La Jolla, California
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Correspondence to: Kurt Wüthrich. E-mail: wuthrich@scripps.edu

Abstract

The domain of unknown function (DUF) YP_001302112.1, a protein secreted by the human intestinal microbita, has been determined by NMR and represents the first structure for the Pfam PF14466. Its NMR structure is classified as a new fold, which, nonetheless, shows limited similarities with representatives of the PLAT/LH2 domains from PF01477 and the C2 domains from PF00168, both of which bind Ca2+ for their physiological functions. Further experiments revealed affinity of YP_001302112.1 for Ca2+, and the NMR structure in the presence of CaCl2 was better defined than that of the apo-protein. Overall, these NMR structures establish a new connection between structural representatives from two widely different Pfams that include the calcium-binding domain of a sialidase from Vibrio cholerae and the α-toxin from Clostridium perfrigens, whereby these two proteins have only 7% sequence identity. Furthermore, it provides information toward the functional annotation of YP_001302112.1, based on its capacity to bind Ca2+, and thus adds to the structural and functional coverage of the protein sequence universe. © 2013 The Protein Society

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