Expression and characterization of the olfactomedin domain of human myocilin.
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.
Nagy
Ildikó
I
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 7, H-1518 Budapest, Hungary.
Trexler
Mária
M
Patthy
László
L
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004220:Disulfides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D005136:Eye Proteins / Q000737:chemistry* / Q000378:metabolism; D005901:Glaucoma / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016366:Open Reading Frames; D010843:Pichia / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D000099179:Myocilin
D003545:Cysteine; D003598:Cytoskeletal Proteins; D004220:Disulfides; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D037102:Lectins; D009419:Nerve Tissue Proteins; D000099179:Myocilin; C081451:olfactomedin