1PVH

Crystal structure of leukemia inhibitory factor in complex with gp130

Summary for 1PVH

• Entry DOI: 10.2210/pdb1pvh/pdb
• Descriptor: Interleukin-6 receptor beta chain, Leukemia inhibitory factor, IODIDE ION, ... (4 entities in total)
• Functional Keywords: cytokine, receptor, signaling, beta sheet, four helix bundle, signaling protein-cytokine complex, signaling protein/cytokine
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P40189; Secreted: P15018
• Total number of polymer chains: 4
• Total formula weight: 83690.83

Authors

Boulanger, M.J.,Bankovich, A.J.,Kortemme, T.,Baker, D.,Garcia, K.C. (deposition date: 2003-06-27, release date: 2003-10-14, Last modification date: 2024-10-30)

Primary citation

Boulanger, M.J.,Bankovich, A.J.,Kortemme, T.,Baker, D.,Garcia, K.C.
Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
Mol.Cell, 12:577-589, 2003

PubMed Abstract: Gp130 is a shared cell-surface signaling receptor for at least ten different hematopoietic cytokines, but the basis of its degenerate recognition properties is unknown. We have determined the crystal structure of human leukemia inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp130 at 2.5 A resolution. Strikingly, we find that the shared binding site on gp130 has an entirely rigid core, while the LIF binding interface diverges sharply in structure and chemistry from that of other gp130 ligands. Dissection of the LIF-gp130 interface, along with comparative studies of other gp130 cytokines, reveal that gp130 has evolved a "thermodynamic plasticity" that is relatively insensitive to ligand structure, to enable crossreactivity. These observations reveal a novel and alternative mechanism for degenerate recognition from that of structural plasticity.

PubMed: 14527405
DOI: 10.1016/S1097-2765(03)00365-4

Experimental method

X-RAY DIFFRACTION (2.5 Å)