Novel fold revealed by the structure of a FAS1 domain pair from the insect cell adhesion molecule fasciclin I.
Fasciclin I is an insect neural cell adhesion molecule consisting of four FAS1 domains, homologs of which are present in many bacterial, plant, and animal proteins. The crystal structure of FAS1 domains 3 and 4 of Drosophila fasciclin I reveals a novel domain fold, consisting of a seven-stranded beta wedge and a number of alpha helices. The two domains are arranged in a linear fashion and interact through a substantial polar interface. Missense mutations in the FAS1 domains of the human protein betaig-h3 cause corneal dystrophies. Many mutations alter highly conserved core residues, but the two most common mutations, affecting Arg-124 and Arg-555, map to exposed alpha-helical regions, suggesting reduced protein solubility as the disease mechanism.
Clout
Naomi J
NJ
Biophysics Section, Department of Biological Sciences, Imperial College, SW7 2AZ, London, United Kingdom.
Tisi
Dominic
D
Hohenester
Erhard
E
D000595:Amino Acid Sequence; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004330:Drosophila / Q000737:chemistry; D016326:Extracellular Matrix Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C051641:fasciclin I