Novel fold revealed by the structure of a FAS1 domain pair from the insect cell adhesion molecule fasciclin I

Structure. 2003 Feb;11(2):197-203. doi: 10.1016/s0969-2126(03)00002-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion Molecules, Neuronal / chemistry*
  • Crystallography, X-Ray
  • Drosophila / chemistry
  • Extracellular Matrix Proteins*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Protein Folding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Transforming Growth Factor beta*


  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • fasciclin I
  • betaIG-H3 protein

Associated data

  • PDB/1O70