title: Structure of the calcium-rich signature domain of human thrombospondin-2.
abstract: Thrombospondins (THBSs) are secreted glycoproteins that have key roles in interactions between cells and the extracellular matrix. Here, we describe the 2.6-A-resolution crystal structure of the glycosylated signature domain of human THBS2, which includes three epidermal growth factor-like modules, 13 aspartate-rich repeats and a lectin-like module. These elements interact extensively to form three structural regions termed the stalk, wire and globe. The THBS2 signature domain is stabilized by these interactions and by a network of 30 bound Ca(2+) ions and 18 disulfide bonds. The structure suggests how genetic alterations of THBSs result in disease.
authors.affiliation: Department of Medicine, 4285B Medical Sciences Center, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA.
authors.forename: C Britt
authors.initials: CB
authors.lastname: Carlson
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bernstein
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Annis
authors.forename: Tina M
authors.initials: TM
authors.lastname: Misenheimer
authors.forename: Blue-leaf A
authors.initials: BL
authors.lastname: Hannah
authors.forename: Deane F
authors.initials: DF
authors.lastname: Mosher
authors.forename: James L
authors.initials: JL
authors.lastname: Keck
mesh_terms: D000595:Amino Acid Sequence; D001847:Bone Diseases / Q000235:genetics; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D006801:Humans; D007592:Joint Diseases / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D019699:Thrombospondins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000099262:Thrombospondin 2
chemical_list: D002118:Calcium; D019699:Thrombospondins; D000099262:Thrombospondin 2