Outline structure of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders

• Published in: The EMBO journal Vol. 15; no. 22; pp. 6050 - 6059
• Main Authors: Bateman, A, Jouet, M, MacFarlane, J, Du, J. S, Kenwrick, S, Chothia, C
• Format: Journal Article
• Language: English
• Published: England 15.11.1996
• Subjects: Amino Acid Sequence; Cell Adhesion Molecules, Neuronal - chemistry; Cell Adhesion Molecules, Neuronal - genetics; Drosophila Proteins; Fibronectins - chemistry; Fibronectins - genetics; Humans; Hydrocephalus - genetics; Leukocyte L1 Antigen Complex; Models, Molecular; Molecular Sequence Data; Muscle Proteins - chemistry; Muscle Proteins - genetics; Mutation - genetics; Myosin-Light-Chain Kinase; Neural Cell Adhesion Molecules - chemistry; Neural Cell Adhesion Molecules - genetics; Peptide Fragments; Peptides; Protein Conformation; Protein Folding; Protein Structure, Secondary; Sequence Alignment; X Chromosome - genetics
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1996.tb00993.x

The L1 cell adhesion molecule has six domains homologous to members of the immunoglobulin superfamily and five homologous to fibronectin type III domains. We determined the outline structure of the L1 domains by showing that they have, at the key sites that determine conformation, residues similar to those in proteins of known structure. The outline structure describes the relative positions of residues, the major secondary structures and residue solvent accessibility. We use the outline structure to investigate the likely effects of 22 mutations that cause neurological diseases. The mutations are not randomly distributed but cluster in a few regions of the structure. They can be divided into those that act mainly by changing conformation or denaturing their domain and those that alter its surface properties.