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Biochemistry. 2013 Nov 12;52(45):8126-38. doi: 10.1021/bi400638s. Epub 2013 Oct 28.

Acetylation of lysine 92 improves the chaperone and anti-apoptotic activities of human αB-crystallin.

Author information

1
Department of Ophthalmology and Visual Sciences and ‡Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.

Abstract

αB-Crystallin is a chaperone and an anti-apoptotic protein that is strongly expressed in many tissues, including the lens, retina, heart, and kidney. In the human lens, several lysine residues in αB-crystallin are acetylated. We have previously shown that such acetylation is predominant at lysine 92 (K92) and lysine 166 (K166). We have investigated the effect of lysine acetylation on the structure and functions of αB-crystallin by the specific introduction of an N(ε)-acetyllysine (AcK) mimic at K92. The introduction of AcK slightly altered the secondary and tertiary structures of the protein. The introduction of AcK also resulted in an increase in the molar mass and hydrodynamic radius of the protein, and the protein became structurally more open and more stable than the native protein. The acetyl protein acquired higher surface hydrophobicity and exhibited 25-55% higher chaperone activity than the native protein. The acetyl protein had more client protein binding per subunit of the protein and higher binding affinity relative to that of the native protein. The acetyl protein was at least 20% more effective in inhibiting chemically induced apoptosis than the native protein. Molecular modeling suggests that acetylation of K92 makes the "α-crystallin domain" more hydrophobic. Together, our results reveal that the acetylation of a single lysine residue in αB-crystallin makes the protein structurally more stable and improves its chaperone and anti-apoptotic activities. Our findings suggest that lysine acetylation of αB-crystallin is an important chemical modification for enhancing αB-crystallin's protective functions in the eye.

PMID:
24128140
PMCID:
PMC3889837
DOI:
10.1021/bi400638s
[Indexed for MEDLINE]
Free PMC Article

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