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

Author(s): Xu, Y; Soo, P; Walker, F; Zhang, HH; Redpath, N; Tan, CW; Nicola, NA; Adams, TE; Garrett, TP; Zhang, JG; Burgess, AW;
Details: Publication Year 2015-05-22,Volume 427,Issue #10,Page 1943-48
Journal Title: J Mol Biol
Publication Type: Journal Article
Abstract: 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.
Publisher: Elsevier
Research Division(s): Structural Biology; Cancer And Haematology
PubMed ID: 25765764
Publisher's Version: https://doi.org/10.1016/j.jmb.2015.03.001
Open Access at Publisher's Site: http://www.sciencedirect.com/science/article/pii/S0022283615001734
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-05-20 10:11:29

Last Modified: 2015-05-20 02:43:03