Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin.
Bone sialoprotein (BSP) and osteopontin (OPN) are two members of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family of genetically related proteins that are clustered on human chromosome 4. We present evidence that this entire family is the result of duplication and subsequent divergent evolution of a single ancient gene. The solution structures of these 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 conformations consistent with them both being completely unstructured in solution. This flexibility appears to enable these relatively small glycoproteins to rapidly associate with a number of different binding partners including other proteins as well as the mineral phase of bones and teeth. These proteins often function by bridging two proteins of fixed structures into a biologically active complex.
Fisher
L W
LW
Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, 20892-4320, USA. lfisher@dir.nidcr.nih.gov
Torchia
D A
DA
Fohr
B
B
Young
M F
MF
Fedarko
N S
NS
D000595:Amino Acid Sequence; D001842:Bone and Bones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008969:Molecular Sequence Data; D053495:Osteopontin; D018583:Pliability; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D012795:Sialoglycoproteins / Q000737:chemistry* / Q000378:metabolism*; D012996:Solutions
C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D016023:Integrins; D008024:Ligands; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D012996:Solutions; D053495:Osteopontin