Carbonyl-metabolizing enzymes and their relatives recruited as structural proteins in the eye lens.
The refractive properties of the eye lens are determined by abundant soluble structural proteins known as crystallins. While some crystallins are common to most vertebrates, others are abundant only in groups of related species. These taxon-specific crystallins all turn out to be enzymes, apparently recruited by modification of gene expression without prior gene duplication. They include eta-crystallin, accounting for up to 25% of protein in elephant shrew lenses and apparently identical to cytoplasmic aldehyde dehydrogenase; rho-crystallin from frog lenses, a member of the same superfamily as aldose and aldehyde reductases; and zeta-crystallin, found in guinea pig and camel lenses, which is structurally related to alcohol dehydrogenase (ADH). Unlike ADH, zeta-crystallin requires NADPH rather than NAD+/NADH as cofactor. Molecular modelling of zeta-crystallin shows that amino-acid changes around the co-factor binding site are responsible for this change in affinity. Purified guinea pig lens zeta-crystallin has a substrate preference for orthoquinones which are reduced by a single electron transfer mechanism. cDNA sequencing of zeta-crystallin suggests that the expression in lens as a crystallin depends on a different gene promoter from that used predominantly in liver. The putative guinea pig zeta-crystallin lens promoter has now been assayed for function in transfection studies. Elements with positive and negative effects on transcription, at least one of which has tissue preferred function, have been defined. When introduced into transgenic mice this promoter exhibits tissue-specific expression in the lens. This is the first identification of a lens-specific, alternative promoter in an enzyme crystallin gene.
Lee
D C
DC
National Eye Institute, NIH, Bethesda, MD 20892.
Gonzalez
P
P
Rao
P V
PV
Zigler
J S
JS
Wistow
G J
GJ
D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003459:Crystallins / Q000235:genetics / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism*; D015394:Molecular Structure; D011401:Promoter Regions, Genetic; D014018:Tissue Distribution
D003459:Crystallins; D000444:Aldehyde Dehydrogenase