LINGO1

2ID5, 4OQT84894235402ENSG00000169783ENSMUSG00000049556Q96FE5Q9D1T0NM_001301194NM_001301195NM_001301197NM_001301198NM_001301199NM_001301200NM_032808NM_001361118NM_001361119NM_001361120NP_001288123NP_001288124NP_001288126NP_001288127NP_001288128NP_001288129NP_116197NP_001348047NP_001348048NP_001348049Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo (neurite outgrowth inhibitor) receptor also known as the reticulon 4 receptor. 2id5: Crystal Structure of the Lingo-1 Ectodomain Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo (neurite outgrowth inhibitor) receptor also known as the reticulon 4 receptor. It has been found that LINGO-1 antagonists such as BIIB033 could significantly improve and regulate survival after neural injury caused by the protein. The human LINGO-1 is a single-pass type 1 transmembrane protein of 614 amino acids. It contains a signal sequence of 34 residues, followed by a LRR (leucine-rich repeat) domain, an Ig (immunoglobulin-like) domain, a stalk domain, a transmembrane region and a short cytoplasmic tail. As a transmembrane protein, it can mostly be found on the cell membrane. The LINGO-1 structure has been shown to be highly stable both in its crystal form and in solution, thanks to its leucine-rich repeat Ig-composite fold. Since the tetramer has a very large surface area into the cell membrane, it is thought that this may serve as an efficient and stable binding platform, facilitating the interaction with NgR, p75, TROY complex. The extracellular domain consists of the signal sequence, 11 LRR motifs comprised between an N-terminal and C-terminal capping domains, and the Immunoglobulin-like (IgC2) domain. The C-terminal LRR domain is essential for the protein's function with its screening for proteins that interact with this domain. The structure, together with biophysical analysis of LINGO-1 properties have revealed that the protein's LRR-Ig composite fold of the protein can drive it to associate with itself in a circular ring-like form, creating a closed and stable tetramer in solution and in crystal. The intracellular part of the protein is formed by the transmembrane region and a cytoplasmic tail of 38 residues. It contains a canonical Epidermal Growth Factor Receptor (EGFR)-like tyrosine phosphorylation site on the 591 residue that is critical for intracellular signals. LINGO-1 is a co-receptor that interacts with the ligand-binding Nogo-66 receptor (NogoR) in the Nogo receptor signaling complex. The Nogo receptor complex is formed when Nogo-66 binds to its receptor. LINGO-1 is an homotetramer which forms a ternary complex with RTN4R/NGFR and RTN4R/TNFRSF19. LINGO-1 contains several N-glycosylation sites that could have a negative effect on its capacity to self-interact with cis or trans, with other partners, or gangliosides. It also contains high-mannose glycans.