2ID5

Crystal Structure of the Lingo-1 Ectodomain

Summary for 2ID5

• Entry DOI: 10.2210/pdb2id5/pdb
• Descriptor: Leucine rich repeat neuronal 6A, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: cns-specific lrr-ig containing, ligand binding protein, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q96FE5
• Total number of polymer chains: 4
• Total formula weight: 227593.97

Authors

Mosyak, L.,Wood, A.,Dwyer, B.,Johnson, M.,Stahl, M.L.,Somers, W.S. (deposition date: 2006-09-14, release date: 2006-09-26, Last modification date: 2020-07-29)

Primary citation

Mosyak, L.,Wood, A.,Dwyer, B.,Buddha, M.,Johnson, M.,Aulabaugh, A.,Zhong, X.,Presman, E.,Benard, S.,Kelleher, K.,Wilhelm, J.,Stahl, M.L.,Kriz, R.,Gao, Y.,Cao, Z.,Ling, H.P.,Pangalos, M.N.,Walsh, F.S.,Somers, W.S.
The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition.
J.Biol.Chem., 281:36378-36390, 2006

PubMed Abstract: Nogo receptor (NgR)-mediated control of axon growth relies on the central nervous system-specific type I transmembrane protein Lingo-1. Interactions between Lingo-1 and NgR, along with a complementary co-receptor, result in neurite and axonal collapse. In addition, the inhibitory role of Lingo-1 is particularly important in regulation of oligodendrocyte differentiation and myelination, suggesting that pharmacological modulation of Lingo-1 function could be a novel approach for nerve repair and remyelination therapies. Here we report on the crystal structure of the ligand-binding ectodomain of human Lingo-1 and show it has a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. The structure, together with biophysical analysis of its solution properties, reveals that in the crystals and in solution Lingo-1 persistently associates with itself to form a stable tetramer and that it is its LRR-Ig-composite fold that drives such assembly. Specifically, in the crystal structure protomers of Lingo-1 associate in a ring-shaped tetramer, with each LRR domain filling an open cleft in an adjacent protomer. The tetramer buries a large surface area (9,200 A2) and may serve as an efficient scaffold to simultaneously bind and assemble the NgR complex components during activation on a membrane. Potential functional binding sites that can be identified on the ectodomain surface, including the site of self-recognition, suggest a model for protein assembly on the membrane.

PubMed: 17005555
DOI: 10.1074/jbc.M607314200

Experimental method

X-RAY DIFFRACTION (2.698 Å)