title: 3D structural conformation and functional domains of polysialyltransferase ST8Sia IV required for polysialylation of neural cell adhesion molecules.
abstract: Synthesis of α2,8-polysialic acid (polySia) glycans are catalyzed by two highly homologous mammalian polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST), which are two members of the ST8Sia gene family of sialytransferases. During polysialylation, both STX and PST catalyze the transfer of multiple Sia residues from the activated sugar nucleotide precursor, CMP-Neu5Ac (Sia), to terminal Sia residues on N- and Olinked oligosaccharide chains on acceptor glycoproteins, including the neural cell adhesion molecule (NCAM), which is the major carrier protein of polySia. Based on our new findings and previously published studies, this review summarizes the present concepts regarding the molecular mechanism underlying regulation of protein-specific polysialylation of NCAM that includes the following: (1) Determination of the catalytic domains and specific regions within ST8Sia IV for recognizing and catalyzing the efficient polysialylation of NCAM; (2) Identification of key amino acid residues within the PSTD motif of ST8Sia IV that are essential for polysialylation; (3) Verification of key amino acids in the PBR domain of ST8Sia IV required for NCAM-specific polysialylation; and (4) a 3D conformational study of ST8Sia IV based on the Phyre2 server to discover the relationship between the structure and its functional domains of the polyST. Based on these results, our 3D model of ST8Sia IV was used to identify and characterize the catalytic domains and amino acid residues critical for catalyzing polysialylation, and have provided new structural information for supporting a detailed mechanism of polyST-NCAM interaction required for polysialylation of NCAM, findings that have not been previously reported.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhou
authors.forename: Ri-Bo
authors.initials: RB
authors.lastname: Huang
authors.affiliation: National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, China. gpzhou@ucdavis.edu.
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Troy
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D012799:Sialyltransferases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; D012799:Sialyltransferases; C515117:ST8SIA4 protein, human