title: Outline structure of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders.
abstract: 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.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bateman
authors.forename: M
authors.initials: M
authors.lastname: Jouet
authors.forename: J
authors.initials: J
authors.lastname: MacFarlane
authors.forename: J S
authors.initials: JS
authors.lastname: Du
authors.forename: S
authors.initials: S
authors.lastname: Kenwrick
authors.forename: C
authors.initials: C
authors.lastname: Chothia
mesh_terms: D000595:Amino Acid Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics; D029721:Drosophila Proteins; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics; D039841:Leukocyte L1 Antigen Complex; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009219:Myosin-Light-Chain Kinase; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics*; D010446:Peptide Fragments; D010455:Peptides; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014960:X Chromosome / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D005353:Fibronectins; D039841:Leukocyte L1 Antigen Complex; D009124:Muscle Proteins; D019006:Neural Cell Adhesion Molecules; D010446:Peptide Fragments; D010455:Peptides; C061745:Nrg protein, Drosophila; C060640:telokin; D009219:Myosin-Light-Chain Kinase