Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution.

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摘要：

Homodimeric bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor β (TGF-β) 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 Å resolution. A common scaffold of BMP-2, BMP-7 and the TGF-βs, i.e. the cystine-knot motif and two finger-like double-stranded β-sheets, can be superimposed with r.m.s. deviations of around 1 Å. In contrast to the TGF-βs, the structure of BMP-2 shows differences in the flexibility of the N terminus and the orientation of the central α-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.

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cost screening in hypertension

DOI：

10.1016/j.jcat.2003.06.001

被引量：

591

年份：

1999