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Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens.

Publication ,  Journal Article
Rao, PV; Huang, QL; Horwitz, J; Zigler, JS
Published in: Biochim Biophys Acta
December 14, 1995

The ocular lens is a transparent organ comprised of a highly concentrated and highly ordered matrix of structural proteins, called crystallins, which are probably the longest lived proteins of the body. Lens transparency is dependent upon maintenance of the short range order of the crystallin matrix. This transparency must be maintained for decades in the absence of normal protein synthesis or repair capacity. We present evidence here that alpha-crystallin, one of the major lens proteins, plays a central role in vivo in stabilizing the other crystallins and preventing uncontrolled aggregation of these progressively modified and aging molecules. alpha-Crystallin has previously been shown to suppress non-specific aggregation of denaturing proteins in simple binary systems through a chaperone-like activity. Our studies using soluble homogenates of monkey lenses demonstrate a strong resistance to heat induced non-specific aggregation when the complete complement of crystallins is present; in contrast, if alpha-crystallin is selectively removed prior to heating, the remaining crystallins undergo extensive non-specific aggregation as indicated by light scattering. When alpha-crystallin is present it complexes with denaturing proteins forming a soluble heavy molecular weight (HMW) fraction but no insolubilization is observed, while when alpha-crystallin is absent there is heavy insolubilization and no HMW formed. When intact monkey lenses were heated it could be demonstrated that soluble HMW was generated. Similar HMW protein appears in vivo in the human lens as a function of age. These findings suggest that the soluble HMW protein present in the human lens is the product of the chaperone-like function of alpha-crystallin and that under physiological conditions alpha-crystallin inhibits the uncontrolled aggregation of damaged proteins, thereby preventing the formation of light scattering centers and opacification of the lens.

Duke Scholars

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

December 14, 1995

Volume

1245

Issue

3

Start / End Page

439 / 447

Location

Netherlands

Related Subject Headings

  • Temperature
  • Molecular Chaperones
  • Macaca mulatta
  • Lens, Crystalline
  • Humans
  • Crystallins
  • Animals
  • 51 Physical sciences
  • 31 Biological sciences
  • 06 Biological Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rao, P. V., Huang, Q. L., Horwitz, J., & Zigler, J. S. (1995). Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens. Biochim Biophys Acta, 1245(3), 439–447. https://doi.org/10.1016/0304-4165(95)00125-5
Rao, P. V., Q. L. Huang, J. Horwitz, and J. S. Zigler. “Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens.Biochim Biophys Acta 1245, no. 3 (December 14, 1995): 439–47. https://doi.org/10.1016/0304-4165(95)00125-5.
Rao PV, Huang QL, Horwitz J, Zigler JS. Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens. Biochim Biophys Acta. 1995 Dec 14;1245(3):439–47.
Rao, P. V., et al. “Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens.Biochim Biophys Acta, vol. 1245, no. 3, Dec. 1995, pp. 439–47. Pubmed, doi:10.1016/0304-4165(95)00125-5.
Rao PV, Huang QL, Horwitz J, Zigler JS. Evidence that alpha-crystallin prevents non-specific protein aggregation in the intact eye lens. Biochim Biophys Acta. 1995 Dec 14;1245(3):439–447.

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

December 14, 1995

Volume

1245

Issue

3

Start / End Page

439 / 447

Location

Netherlands

Related Subject Headings

  • Temperature
  • Molecular Chaperones
  • Macaca mulatta
  • Lens, Crystalline
  • Humans
  • Crystallins
  • Animals
  • 51 Physical sciences
  • 31 Biological sciences
  • 06 Biological Sciences