4mid

Crystal Structure of Activin A/BMP2 chimeraCrystal Structure of Activin A/BMP2 chimera

Structural highlights 4mid is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.139Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function INHBA_HUMAN Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.BMP2_HUMAN Induces cartilage and bone formation. Publication Abstract from PubMed Recombinant Bone Morphogenetic Protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10-fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 A that reveals a distinct BMP2-like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100-fold greater than that of BMP2. The structure also led to our identification of a single Activin A-derived amino acid residue which when mutated to the corresponding BMP2 residue resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non-union bone fractures. (c) 2014 American Society for Bone and Mineral Research. An Activin A/BMP2 Chimera Displays Bone Healing Properties Superior to Those of BMP2.,Yoon BH, Esquivies L, Ahn C, Gray PC, Ye SK, Kwiatkowski W, Choe S J Bone Miner Res. 2014 Apr 1. doi: 10.1002/jbmr.2238. PMID:24692083 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bone morphogenetic protein 3D structures

spinqualitylabelsall models 4mid, resolution 2.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image