4u7m

From Proteopedia

LRIG1 extracellular domain: Structure and Function Analysis

PDB ID 4u7m

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Structural highlights

4u7m 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 2.757Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LRIG1_HUMAN Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation.^[1]

Publication Abstract from PubMed

We have expressed and purified three soluble fragments of the human LRIG1-ECD (extracellular domain): the LRIG1-LRR (leucine-rich repeat) domain, the LRIG1-3Ig (immunoglobulin-like) domain, and the LRIG1-LRR-1Ig fragment using baculovirus vectors in insect cells. The two LRIG1 domains crystallised so that we have been able to determine the three-dimensional structures at 2.3A resolution. We developed a three-dimensional structure for the LRIG1-ECD using homology modelling based on the LINGO-1 structure. The LRIG1-LRR domain and the LRIG1-LRR-1Ig fragment are monomers in solution, whereas the LRIG1-3Ig domain appears to be dimeric. We could not detect any binding of the LRIG1 domains or the LRIG1-LRR-1Ig fragment to the EGF receptor (EGFR), either in solution using biosensor analysis or when the EGFR was expressed on the cell surface. The FLAG-tagged LRIG1-LRR-1Ig fragment binds weakly to colon cancer cells regardless of the presence of EGFRs. Similarly, neither the soluble LRIG1-LRR nor the LRIG1-3Ig domains nor the full-length LRIG1 co-expressed in HEK293 cells inhibited ligand-stimulated activation of cell-surface EGFR.

LRIG1 Extracellular Domain: Structure and Function Analysis.,Xu Y, Soo P, Walker F, Zhang HH, Redpath N, Tan CW, Nicola NA, Adams TE, Garrett TP, Zhang JG, Burgess AW J Mol Biol. 2015 Mar 9. pii: S0022-2836(15)00173-4. doi:, 10.1016/j.jmb.2015.03.001. PMID:25765764^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gur G, Rubin C, Katz M, Amit I, Citri A, Nilsson J, Amariglio N, Henriksson R, Rechavi G, Hedman H, Wides R, Yarden Y. LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. EMBO J. 2004 Aug 18;23(16):3270-81. Epub 2004 Jul 29. PMID:15282549 doi:http://dx.doi.org/10.1038/sj.emboj.7600342
↑ Xu Y, Soo P, Walker F, Zhang HH, Redpath N, Tan CW, Nicola NA, Adams TE, Garrett TP, Zhang JG, Burgess AW. LRIG1 Extracellular Domain: Structure and Function Analysis. J Mol Biol. 2015 Mar 9. pii: S0022-2836(15)00173-4. doi:, 10.1016/j.jmb.2015.03.001. PMID:25765764 doi:http://dx.doi.org/10.1016/j.jmb.2015.03.001