Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin

Bone sialoprotein (BSP) and osteopontin (OPN) are two members of the SIBLIN G (Small Integrin-Binding LIgand, N-linked Glycoprotein) family of genetica lly related proteins that are clustered on human chromosome 4. We present e vidence that this entire family is the result of duplication and subsequent divergent evolution of a single ancient gene. The solution structures of t hese two post-translationally modified recombinant proteins were solved by one dimensional proton NMR and transverse relaxation times. The polypeptide backbones of both free BSP and OPN rapidly sample an ensemble of conformat ions consistent with them both being completely unstructured in solution. T his flexibility appears to enable these relatively small glycoproteins to r apidly associate with a number of different binding partners including othe r proteins as well as the mineral phase of bones and teeth. These proteins often function by bridging two proteins of fixed structures into a biologic ally active complex. (C) 2001 Academic Press.