1REW

Structural refinement of the complex of bone morphogenetic protein 2 and its type IA receptor

Summary for 1REW

• Entry DOI: 10.2210/pdb1rew/pdb
• Related: 1ES7 1REU 3BMP
• Descriptor: bone morphogenetic protein 2, bone morphogenetic protein receptor type IA (3 entities in total)
• Functional Keywords: tgf-beta fold; bria-fold; 3-finger toxin fold, hormone-growth factor-signaling protein complex, hormone/growth factor/signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 55196.61

Authors

Keller, S.,Nickel, J.,Zhang, J.-L.,Sebald, W.,Mueller, T.D. (deposition date: 2003-11-07, release date: 2004-05-04, Last modification date: 2024-10-30)

Primary citation

Keller, S.,Nickel, J.,Zhang, J.L.,Sebald, W.,Mueller, T.D.
Molecular recognition of BMP-2 and BMP receptor IA.
Nat.Struct.Mol.Biol., 11:481-488, 2004

PubMed Abstract: Bone morphogenetic protein-2 (BMP-2) and other members of the TGF-beta superfamily regulate the development, maintenance and regeneration of tissues and organs. Binding epitopes for these extracellular signaling proteins have been defined, but hot spots specifying binding affinity and specificity have so far not been identified. In this study, mutational and structural analyses show that epitopes of BMP-2 and the BRIA receptor form a new type of protein-protein interface. The main chain atoms of Leu 51 and Asp53 of BMP-2 represent a hot spot of binding to BRIA. The BMP-2 variant L51P was deficient in type I receptor binding only, whereas its overall structure and its binding to type II receptors and modulator proteins, such as noggin, were unchanged. Thus, the L51P substitution converts BMP-2 into a receptor-inactive inhibitor of noggin. These results are relevant for other proteins of the TGF-beta superfamily and provide useful clues for structure-based drug design.

PubMed: 15064755
DOI: 10.1038/nsmb756

Experimental method

X-RAY DIFFRACTION (1.863 Å)