| Abstract: | 3D‐Rapid Prototyping (3D‐RP) is a novel technique for the construction of highly accurate three‐dimensional polyamide models of biomolecules. This method has been shown to be a valuable tool in the modeling of protein‐protein‐interactions as well as in the analysis of surface topography. Using this technique we were recently able to identify a so far unknown structure on the concave side of bone morphogenetic protein 2 (BMP‐2). Since this structure is the imprint of a left‐handed helix we have called this negative an unthelix. Obviously this novel structural feature of BMP‐2 may act as a binding side for endogenous ligands. BMP‐2 belongs to the highly conserved Transforming Growth Factor‐β (TGF‐β) superfamily, a large group of multifunctional peptides controlling differentiation, proliferation and repair in multicellular organism. The protomer structures of all members share a cystine‐knot motif as a characteristic feature. The question therefore arose whether a) the novel anthelical motif found in BMP‐2 is a common structural feature of this family and b) if there are any differences in terms of pitch and radius of the anthelix. As anthelical structures are difficult to visualize and nearly impossible to quantify using 3D molecular visualization software we constructed models of BMP‐2, BMP‐7 and TGF‐β2 from X‐ray crystallographic data by 3D‐Rapid Prototyping (3D‐RP). The anthelix motif was found in BMP‐2, BMP‐7 and TGF‐β2 with similar values for pitch (ca. 8‐10 nm) and radius (ca. 0.5‐0.7 nm). In contrast the anthelical motif was not found in a 3D‐RP model of human chorionic gonadotropin (HCG) which is also a member of the cystine‐knot family but doesn’t belong to the TGF‐β superfamily. These results were corroborated by measurements of the intersubunit angle of these dimeric proteins (141‐149°) and the distances between the center of mass (1.68‐1.96 nm) of the subunits both of which appear to be determinants of the anthelical pitch. We conclude that the anthelical groove on the concave side is a common structural motif of BMP‐2, BMP‐7 and TGF‐β2 and maybe of the whole group of the TGF‐β superfamily. |
