1S4Y

Crystal structure of the activin/actrIIb extracellular domain

Summary for 1S4Y

• Entry DOI: 10.2210/pdb1s4y/pdb
• Descriptor: Activin receptor type IIB precursor, Inhibin beta A chain (3 entities in total)
• Functional Keywords: structural genomics, jcsg, transferase, psi, protein structure initiative, joint center for structural genomics
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P27040; Secreted: P08476
• Total number of polymer chains: 4
• Total formula weight: 49131.08

Authors

Greenwald, J.,Vega, M.E.,Allendorph, G.P.,Fischer, W.H.,Vale, W.,Choe, S.,Joint Center for Structural Genomics (JCSG) (deposition date: 2004-01-19, release date: 2004-08-10, Last modification date: 2024-11-13)

Primary citation

Greenwald, J.,Vega, M.E.,Allendorph, G.P.,Fischer, W.H.,Vale, W.,Choe, S.
A Flexible Activin Explains the Membrane-Dependent Cooperative Assembly of TGF-beta Family Receptors.
Mol.Cell, 15:485-489, 2004

PubMed Abstract: A new crystal structure of activin in complex with the extracellular domain of its type II receptor (ActRIIb-ECD) shows that the ligand exhibits an unexpected flexibility. The motion in the activin dimer disrupts its type I receptor interface, which may account for the disparity in its affinity for type I versus type II receptors. We have measured the affinities of activin and its antagonist inhibin for ActRIIb-ECD and found that the affinity of the 2-fold symmetric homodimer activin for ActRIIb-ECD depends on the availability of two spatially coupled ActRIIb-ECD molecules, whereas the affinity of the heterodimer inhibin does not. Our results indicate that activin's affinity for its two receptor types is greatly influenced by their membrane-restricted setting. We propose that activin affinity is modulated by the ligand flexibility and that cooperativity is achieved by binding to two ActRII chains that immobilize activin in a type I binding-competent orientation.

PubMed: 15304227
DOI: 10.1016/j.molcel.2004.07.011

Experimental method

X-RAY DIFFRACTION (2.3 Å)