Zn2+ enhances the molecular chaperone function and stability of alpha-crystallin.


Abstract

Alpha-crystallin, the major eye lens protein, is a molecular chaperone that plays a crucial role in the suppression of protein aggregation and thus in the long-term maintenance of lens transparency. Zinc is a micronutrient of the eye, but its molecular interaction with alpha-crystallin has not been studied in detail. In this paper, we present results of in vitro experiments that show bivalent zinc specifically interacts with alpha-crystallin with a dissociation constant in the submillimolar range (Kd approximately 0.2-0.4 mM). We compared the effect of Zn2+ with those of Ca2+, Cu2+, Mg2+, Cd2+, Pb2+, Ni2+, Fe2+, and Co2+ at 1 mM on the structure and chaperoning ability of alpha-crystallin. An insulin aggregation assay showed that among the bivalent metal ions, only 1 mM Zn2+ improved the chaperone function of alpha-crystallin by 30% compared to that in the absence of bivalent metal ions. Addition of 1 mM Zn2+ increased the yield of alpha-crystallin-assisted refolding of urea-treated LDH to its native state from 33 to 38%, but other bivalent ions had little effect. The surface hydrophobicity of alpha-crystallin was increased by 50% due to the binding of Zn2+. In the presence of 1 mM Zn2+, the stability of alpha-crystallin was enhanced by 36 kJ/mol, and it became more resistant to tryptic cleavage. The implications of enhanced stability and molecular chaperone activity of alpha-crystallin in the presence of Zn2+ are discussed in terms of its role in the long-term maintenance of lens transparency and cataract formation. Study holds ProTherm entries: 23100, 23101, 23102, 23103, 23104, 23105, 23106, 23107, 23108, 23109, 23110, 23111, 23112, 23113, 23114 Extra Details: Native to Intermediate alpha-Crystallin, Zn2+, Chaperone Function, Stability, bivalent metal ions.

Submission Details

ID: 7ze4A7n83

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:54 p.m.

Version: 1

Publication Details
Biswas A;Das KP,Biochemistry (2008) Zn2+ enhances the molecular chaperone function and stability of alpha-crystallin. PMID:18095658
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
2KLR 2009-07-08T00:00:00+0000 0 Solid-state NMR structure of the alpha-crystallin domain in alphaB-crystallin oligomers
2N0K 2015-03-09T00:00:00+0000 0 Chemical shift assignments and structure of the alpha-crystallin domain from human, HSPB5
2WJ7 2009-05-22T00:00:00+0000 2.63 human alphaB crystallin
2Y1Y 2010-12-10T00:00:00+0000 2.0 Human alphaB crystallin ACD(residues 71-157)
2Y1Z 2010-12-10T00:00:00+0000 2.5 Human alphaB Crystallin ACD R120G
2Y22 2010-12-13T00:00:00+0000 3.7 Human AlphaB-crystallin Domain (residues 67-157)
2YGD 2011-04-13T00:00:00+0000 9.4 Molecular architectures of the 24meric eye lens chaperone alphaB- crystallin elucidated by a triple hybrid approach
3J07 2011-04-27T00:00:00+0000 20.0 Model of a 24mer alphaB-crystallin multimer
3L1G 2009-12-11T00:00:00+0000 3.32 Human AlphaB crystallin
3SGM 2011-06-15T00:00:00+0000 1.7 Bromoderivative-2 of amyloid-related segment of alphaB-crystallin residues 90-100

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
96.6 Alpha-crystallin B chain Q9EPF3 CRYAB_SPAJD
96.6 Alpha-crystallin B chain P05811 CRYAB_MESAU
97.1 Alpha-crystallin B chain P23928 CRYAB_RAT
97.1 Alpha-crystallin B chain Q5ENY9 CRYAB_SHEEP
97.1 Alpha-crystallin B chain Q7M2W6 CRYAB_PIG
97.7 Alpha-crystallin B chain P23927 CRYAB_MOUSE
97.7 Alpha-crystallin B chain P02510 CRYAB_BOVIN
98.3 Alpha-crystallin B chain P41316 CRYAB_RABIT
99.4 Alpha-crystallin B chain Q60HG8 CRYAB_MACFA
100.0 Alpha-crystallin B chain Q5R9K0 CRYAB_PONAB
100.0 Alpha-crystallin B chain P02511 CRYAB_HUMAN