The binding of von Willebrand factor type C domains of Chordin family proteins to BMP-2 and Tsg is mediated by their SD1 subdomain.
The VWC domain of Chordin family proteins consists of subdomains SD1 and SD2. In previous experiments with VWC1 from CV-2 SD-1 was shown to be crucial for BMP interaction. Now the SD1 from VWC1 and VWC3 of Chordin and CHL2 were established to confer BMP affinity and specificity to these proteins also. In addition, these SD1 subdomains are mediating binding to Tsg. Mutational analysis revealed similar binding epitopes of the various SD1 proteins for BMP-2 and Tsg. Inhibitory activity of CHL2 in C2C12 cells is reduced by mutations in SD1 of VWC1 and even more of VWC3. These results together provide strong evidence that the SD1 subdomain module of about 40 residues represents the crucial binding partner for BMPs and Tsg in these Chordin family proteins and likely in other BMP-binding VWC domains also.
Fujisawa
Takuo
T
Department of Physiological Chemistry II, University of Wuerzburg, Am Hubland, Wuerzburg, Germany.
Huang
Yi
Y
Sebald
Walter
W
Zhang
Jin-Li
JL
D000595:Amino Acid Sequence; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D014841:von Willebrand Factor / Q000737:chemistry*
D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; C481985:Chrdl2 protein, mouse; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C473561:twisted gastrulation protein, mouse; D014841:von Willebrand Factor; C054234:chordin