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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.

SUBMITTER: Carlson CB

PROVIDER: S-EPMC2219892 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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Structure of the calcium-rich signature domain of human thrombospondin-2.

Carlson C Britt CB Bernstein Douglas A DA Annis Douglas S DS Misenheimer Tina M TM Hannah Blue-leaf A BL Mosher Deane F DF Keck James L JL

Nature structural & molecular biology 20050925 10

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 t ...[more]

PMID: 16186819

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