7mrz

Structure of GDF11 bound to fused ActRIIB-ECD and Alk4-ECD with Anti-ActRIIB Fab fragment

spinqualitylabelsall models 7mrz, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7mrz is a 4 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 3Å Ligands: NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GDF11_HUMAN Secreted signal that acts globally to specify positional identity along the anterior/posterior axis during development. Play critical roles in patterning both mesodermal and neural tissues and in establishing the skeletal pattern. Publication Abstract from PubMed The 30+ unique ligands of the TGFbeta family signal by forming complexes using different combinations of type I and type II receptors. Therapeutically, the extracellular domain of a single receptor fused to an Fc molecule can effectively neutralize subsets of ligands. Increased ligand specificity can be accomplished by using the extracellular domains of both the type I and type II receptor to mimic the naturally occurring signaling complex. Here, we report the structure of one "type II-type I-Fc" fusion, ActRIIB-Alk4-Fc, in complex with two TGFbeta family ligands, ActA, and GDF11, providing a snapshot of this therapeutic platform. The study reveals that extensive contacts are formed by both receptors, replicating the ternary signaling complex, despite the inherent low affinity of Alk4. Our study shows that low-affinity type I interactions support altered ligand specificity and can be visualized at the molecular level using this platform. Structures of activin ligand traps using natural sets of type I and type II TGFbeta receptors.,Goebel EJ, Kattamuri C, Gipson GR, Krishnan L, Chavez M, Czepnik M, Maguire MC, Grenha R, Hakansson M, Logan DT, Grinberg AV, Sako D, Castonguay R, Kumar R, Thompson TB iScience. 2021 Dec 9;25(1):103590. doi: 10.1016/j.isci.2021.103590. eCollection , 2022 Jan 21. PMID:35005539 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Growth differentiation factor 3D STRUCTURES

Proteopedia Page Contributors and Editors (what is this?)

OCA