LRIG1 extracellular domain: structure and function analysis

Journal of Molecular Biology
Yibin XuAntony W Burgess

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 2.3Å 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.

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Citations

Mar 1, 2016·Scientific Reports·Keiko MaedaMasahide Takahashi
May 10, 2018·Scientific Reports·Shaniya AbudureyimuMasahide Takahashi
Dec 31, 2019·Journal of Immunology Research·Chiara CattaneoMaria Cavaletto
Aug 12, 2016·Molecular Medicine Reports·Zhi-Yuan DengZhan-Gui Tang

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