PMID- 10217480
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20191103
IS  - 1350-9462 (Print)
IS  - 1350-9462 (Linking)
VI  - 18
IP  - 4
DP  - 1999 Jul
TI  - Alpha-crystallin as a molecular chaperone.
PG  - 463-509
AB  - The role of alpha-crystallin as a molecular chaperone may explain how the lens
      stays transparent for so long. Alpha-crystallin prevents the aggregation of other
      lens crystallins and proteins that have become unfolded by "trapping" the protein
      in a high molecular weight complex. It also protects enzyme activities. The
      substrate protein may interact while in a molten globule state. Alpha-crystallin 
      predominantly binds to proteins very early in the denaturation pathways. The
      amphiphilic nature of alpha-crystallin, a polar C-terminal-region and a
      hydrophobic N-terminal-region are all essential for chaperone function. The
      flexible C-terminal extension maintains solubility and can bind to opposing
      charged residues of unfolding proteins. Hydrophobic regions in the N-terminal
      region then hold the unfolded protein. Specific areas important for chaperone
      binding and function have been identified throughout the N-terminal-region,
      connecting peptide and C-terminal extension. After a substantial amount of
      chemical data and models, cryo-EM images of alpha-crystallin have confirmed a
      variable 3D surface with a hollow interior. Alpha-crystallin taken from the lens 
      nucleus shows an age-dependent decrease in chaperone function. High molecular
      weight aggregates and alpha-crystallin found within the nucleus from clear and
      cataract lenses have reduced chaperone function. Post-translational
      modifications, known to occur during ageing, such as glycation, carbamylation,
      oxidation, phosphorylation and truncation cause a decrease in chaperone function.
      Alpha-crystallin is expressed outside the lens. AlphaB-crystallin can be induced 
      by heat shock in many tissues where it is translocated from cytoplasm to nucleus.
      Increased expression of alphaB-crystallin has been seen in many pathological
      states. Conformational disorders, including cataract may have a common aetiology 
      and potentially a common therapy.
FAU - Derham, B K
AU  - Derham BK
AD  - Nuffield Laboratory of Ophthalmology, University of Oxford, UK.
FAU - Harding, J J
AU  - Harding JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Prog Retin Eye Res
JT  - Progress in retinal and eye research
JID - 9431859
RN  - 0 (Crystallins)
RN  - 0 (Molecular Chaperones)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cattle
MH  - Crystallins/*chemistry/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Chaperones/*chemistry/*metabolism
MH  - Molecular Sequence Data
MH  - *Protein Conformation
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
RF  - 306
EDAT- 1999/04/27 00:00
MHDA- 1999/04/27 00:01
CRDT- 1999/04/27 00:00
PHST- 1999/04/27 00:00 [pubmed]
PHST- 1999/04/27 00:01 [medline]
PHST- 1999/04/27 00:00 [entrez]
AID - S1350946298000305 [pii]
AID - 10.1016/s1350-9462(98)00030-5 [doi]
PST - ppublish
SO  - Prog Retin Eye Res. 1999 Jul;18(4):463-509. doi: 10.1016/s1350-9462(98)00030-5.