title: Heparin binds to the laminin alpha4 chain LG4 domain at a site different from that found for other laminins.
abstract: We previously reported that the LG4 domain of the laminin alpha4 chain is responsible for high-affinity heparin binding. To specify the amino acid residues involved in this activity, we produced a series of alpha4 LG4-fusion proteins in which each of the 27 basic residues (arginine, R; histidine; lysine, K) were replaced one by one with alanine (A). When the effective residues R1520A, K1531A, K1533A, and K1539A are mapped on a structural model, they form a track on the concave surface of the beta-sandwich, suggesting that they interact with adjacent sulfate groups along the heparin chain. Whereas low-affinity heparin-binding sites of other LG domains have been located at the top of the beta-sheet sandwich opposite the N and C termini, the residues for high-affinity heparin binding of alpha4 LG4 reveal a new topological area of the LG module.
authors.affiliation: Graduate Courses for Regulation of Biological Signals, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yamashita
authors.forename: Konrad
authors.initials: K
authors.lastname: Beck
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000378:metabolism*; D001665:Binding Sites; D005982:Glutathione Transferase / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000925:Anticoagulants; C501370:Lama4 protein, mouse; D007797:Laminin; D011993:Recombinant Fusion Proteins; C084098:laminin A; D006493:Heparin; D005982:Glutathione Transferase