Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva
Chaikuad A., Alfano I., Kerr G., Sanvitale CE., Boergermann JH., Triffitt JT., Von Delft F., Knapp S., Knaus P., Bullock AN.
Background: Mutations in the ALK2 kinase cause extraskeletal bone formation. Results: We solved the structure of ALK2 in complex with the inhibitor FKBP12. Conclusion: Disease mutations break critical interactions that stabilize the inactive ALK2-FKBP12 complex leading to kinase activation. Significance: We offer an explanation for the effects of mutation and a structural template for the design of small molecule inhibitors. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.