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Author(s): Scheufler C; Sebald W; Hulsmeyer M
Title: Crystal structure of human bone morphogenetic protein-2 at 2.7 angstrom resolution
Source: JOURNAL OF MOLECULAR BIOLOGY 287 (1): 103-115
Date: 1999 MAR 19
Document Type: Journal : Article
DOI:
Language: English
Comment:
Address: Univ Wurzburg, D-97074 Wurzburg, Germany.
Reprint: Sebald, W, Univ Wurzburg, D-97074 Wurzburg, Germany.
E-mail: sebald@biozentrum.uni-wuerzburg.de
Abstract: Homodimeric bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor beta (TGF-beta) superfamily that induces bone formation and regeneration, and determines important steps during early stages of embryonic development in vertebrates and non-vertebrates. BMP-2 can interact with two types of receptor chains, as well as with proteins of the extracellular matrix and several regulatory proteins. We report here the crystal structure of human BMP-2 determined by molecular replacement and refined to an R-value of 24.2% at 2.7 Angstrom resolution. A common scaffold of BMP-2, BMP-7 and the TGP-beta s, i.e. the cystine-knot motif and two finger-like double-stranded beta-sheets, can be superimposed with r.m.s. deviations of around 1 Angstrom. In contrast to the TGF-beta s, the structure of BMP-2 shows differences in the flexibility of the N terminus and the orientation of the central a-helix as well as two external loops at the fingertips with respect to the scaffold. This is also known from the BMP-7 model. Small secondary structure elements in the loop regions of BMP-2 and BMP-7 seem to be specific for the respective BMP-subgroup. Two identical helix-finger clefts and two distinct cavities located around the central 2-fold axis of the dimer show characteristic shapes, polarity and surface charges. The possible function of these specific features in the interaction of BMP-2 with its binding partners is discussed. (C) 1999 Academic Press.
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