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

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