Structural highlights
Disease
[LIFR_HUMAN] Defects in LIFR are the cause of Stueve-Wiedemann syndrome (SWS) [MIM:601559]; also knowns as Schwartz-Jampel syndrome type 2 (SJS2). SWS is a severe autosomal recessive condition and belongs to the group of the bent-bone dysplasias. SWS is characterized by bowing of the lower limbs, with internal cortical thickening, wide metaphyses with abnormal trabecular pattern, and camptodactyly. Additional features include feeding and swallowing difficulties, as well as respiratory distress and hyperthermic episodes, which cause death in the first months of life. The rare survivors develop progressive scoliosis, spontaneous fractures, bowing of the lower limbs, with prominent joints and dysautonomia symptoms, including temperature instability, absent corneal and patellar reflexes, and smooth tongue.[1] Note=A chromosomal aberration involving LIFR is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(5;8)(p13;q12) with PLAG1.
Function
[LIFR_HUMAN] Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
gp130 is a shared receptor for at least nine cytokines and can signal either as a homodimer or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here, we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-Ralpha). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6Ralpha hexameric complex, CNTF/CNTF-Ralpha heterodimerizes gp130 and LIF-R via noncooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic analysis of the full-length gp130/LIF-R/CNTF-Ralpha/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the "tall" class of gp130 family cytokine receptor complexes including LIF, IL-27, IL-12, and others.
Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex.,Skiniotis G, Lupardus PJ, Martick M, Walz T, Garcia KC Mol Cell. 2008 Sep 5;31(5):737-48. PMID:18775332[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dagoneau N, Scheffer D, Huber C, Al-Gazali LI, Di Rocco M, Godard A, Martinovic J, Raas-Rothschild A, Sigaudy S, Unger S, Nicole S, Fontaine B, Taupin JL, Moreau JF, Superti-Furga A, Le Merrer M, Bonaventure J, Munnich A, Legeai-Mallet L, Cormier-Daire V. Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome. Am J Hum Genet. 2004 Feb;74(2):298-305. Epub 2004 Jan 21. PMID:14740318 doi:S0002-9297(07)61840-0
- ↑ Skiniotis G, Lupardus PJ, Martick M, Walz T, Garcia KC. Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex. Mol Cell. 2008 Sep 5;31(5):737-48. PMID:18775332 doi:10.1016/j.molcel.2008.08.011
