Structure and Dynamics of the Fish Eye Lens Protein, gammaM7-crystallin
- Authors
- Mahler, B., Chen, Y., Ford, J., Thiel, C., Wistow, G., and Wu, Z.
- ID
- ZDB-PUB-130425-14
- Date
- 2013
- Source
- Biochemistry 52(20): 3579-87 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Mice
- Models, Molecular
- Molecular Sequence Data
- Protein Conformation
- Protein Folding
- Structure-Activity Relationship
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/metabolism
- gamma-Crystallins/chemistry*
- gamma-Crystallins/metabolism
- PubMed
- 23597261 Full text @ Biochemistry
The vertebrate eye lens contains high concentrations of crystallins. The dense lenses of fish are particularly abundant in a class called γM-crystallin whose members are characterized by an unusually high methionine content and partial loss of the four tryptophan residues conserved in all γ-crystallins from mammals which are proposed to contribute to protection from UV-damage. Here we present the structure and dynamics of γM7-crystallin from zebrafish (Danio rerio). The solution structure shares the typical two-domain, four Greek-key motif arrangement of other γ-crystallins, with the major difference noted in the final loop of the N-terminal domain, spanning residues 65-72. This is likely due to the absence of the conserved tryptophans. Many of the methionine residues are exposed on the surface but are mostly well-ordered and frequently have contacts with aromatic side chains. This may contribute to specialized surface properties of these proteins that exist under high molecular crowding in the fish lens. NMR relaxation data show increased backbone conformational motions in the loop regions of γM7 compared to mouse γS-crystallin, and that fast internal motion of the interdomain linker in γ-crystallins correlates with linker length. Unfolding studies monitored by tryptophan fluorescence confirms results from mutant mouse γS-crystallin that unfolding of a βγ-crystallin domain likely starts from unfolding of the variable loop containing the more fluorescently quenched tryptophan residue, resulting in a native-like unfolding intermediate.