Expression and characterization of the olfactomedin domain of human myocilin

Biochem Biophys Res Commun. 2003 Mar 14;302(3):554-61. doi: 10.1016/s0006-291x(03)00198-0.

Abstract

The olfactomedin-domain has been first identified in olfactomedin, an extracellular matrix protein of the olfactory neuroepithelium. Members of this extracellular domain-family have since been shown to be present in several metazoan proteins, such as latrophilins, myocilins, and noelins, but their biological function is unknown. The olfactomedin-domain of myocilin is of considerable interest, since mutations affecting this domain are associated with primary open angle glaucoma. In order to define structural features of this domain-type we have expressed the olfactomedin-domain of human myocilin in Pichia pastoris. The olfactomedin-domain contains a single disulphide-bond connecting Cys-245 and Cys-433 residues; secondary structure predictions and circular dichroism studies indicate that it consists primarily of beta-strands. It is noteworthy that the majority of mutations associated with severe forms of glaucoma affect residues that reside in conserved secondary structural elements of the olfactomedin-domain or are otherwise critical for the integrity of this protein-fold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Circular Dichroism
  • Cysteine / chemistry
  • Cysteine / metabolism
  • Cytoskeletal Proteins
  • Disulfides / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Extracellular Matrix Proteins / chemistry*
  • Eye Proteins / chemistry*
  • Eye Proteins / metabolism
  • Glaucoma / metabolism
  • Glycoproteins / chemistry*
  • Glycoproteins / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Lectins / metabolism
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Open Reading Frames
  • Pichia / metabolism
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid

Substances

  • Cytoskeletal Proteins
  • Disulfides
  • Extracellular Matrix Proteins
  • Eye Proteins
  • Glycoproteins
  • Immunoglobulins
  • Lectins
  • Nerve Tissue Proteins
  • olfactomedin
  • trabecular meshwork-induced glucocorticoid response protein
  • Cysteine