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Sci. STKE, 5 November 2002
Vol. 2002, Issue 157, p. tw410
[DOI: 10.1126/stke.2002.157.tw410]


Extracellular Matrix The Face of a Thrombospondin Repeat

Matricellular proteins are extracellular matrix-based signaling molecules that play major roles in diverse processes such as wound healing, angiogenesis, cell proliferation, and migration. Thrompospondin-1 (TSP-1) is the prototypical member of this family and exerts its myriad effects by bringing together cytokines, growth factors, other matrix proteins, and membrane proteins. A possible key to understanding its diverse functions is to elucidate the structure of a critical domain called the thrombospondin repeat (TSR). Tan et al. have now determined the three-dimensional structure of two adjacent TSRs in human TSP-1 by x-ray crystallography. The study reveals that each TSR is a highly structured domain of three antiparallel strands held together by interlocking stacks of side chains from alternating tryptophan and arginine residues, all sandwiched between two cysteine disulfides. The domain forms a DNA-like right-handed spiral groove that is positively charged. This "recognition face" may account for the high affinity of TSRs with negatively charged regions of binding partners. It is noteworthy that the TSR domain has been found in multiple different protein families involved in cell migration and tissue remodeling. The architecture may explain the diverse nature of TSR-containing proteins.

K. Tan, M. Duquette, J. Liu, Y. Dong, R. Zhang, A. Joachimiak, J. Lawler, J. Wang Crystal structure of the TSP-1 type 1 repeats: A novel layered fold and its biological implication. J. Cell Biol. 159, 373-382 (2002). [Abstract] [Full Text]

Citation: The Face of a Thrombospondin Repeat. Sci. STKE 2002, tw410 (2002).

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