Structure of the calcium-rich signature domain of human thrombospondin-2.
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.
Carlson
C Britt
CB
Department of Medicine, 4285B Medical Sciences Center, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA.
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
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
D002118:Calcium; D019699:Thrombospondins; D000099262:Thrombospondin 2