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Structure–function relationship of α-crystallin in the context of vertebrate lens evolution and its role in eye disorders

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α- Crystallin, an oligomeric major constituent protein of the eye lens of vertebrates, was originally identified for its role in the lens’ transparency. In addition to having its micelle-like architecture, this protein has molecular chaperoning activity. Lens α-crystallin consists of two subunits, αA and αB, whose aggregate formation is necessary for molecular chaperoning activity. Isolation and characterization of α-crystallin from a wide range of vertebrates will help in understanding a better structure–function relationship in a broader sense, which is yet to be achieved. The stability, structure, aggregation and molecular chaperone activity of α-crystallin differ significantly from species to species. These differences clearly reflect specific structural changes of the protein, which, in turn, may contribute to the transparency and refractive power of the eye lens. Several eye diseases, such as diabetic retinopathy involve oxidative stress, followed by a decrease in total soluble lens proteins and a decreased amount of βB1 crystallins. Intraperitoneal injection of edaravone drugs, a member of the substituted 2-pyrazolin-5-one class, and its analogs are now being tried to revert back crystallin activity and inhibit hyperglycemia and oxidative stress-mediated eye cell damage. In the upcoming future, edaravone-like drugs or their analogs can be synthesized and targeted for better efficacy.
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Journal of Proteins and Proteomics
https://doi.org/10.1007/s42485-022-00101-5
REVIEW
Structure–function relationship ofα‑crystallin inthecontext
ofvertebrate lens evolution andits role ineye disorders
AparajitaChakraborty1· PriyankaDe1· SudipaSaha1,2
Received: 2 August 2022 / Revised: 2 November 2022 / Accepted: 18 November 2022
© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2022
Abstract
α- Crystallin, an oligomeric major constituent protein of the eye lens of vertebrates, was originally identified for its role in
the lens’ transparency. In addition to having its micelle-like architecture, this protein has molecular chaperoning activity.
Lens α-crystallin consists of two subunits, αA and αB, whose aggregate formation is necessary for molecular chaperoning
activity. Isolation and characterization of α-crystallin from a wide range of vertebrates will help in understanding a better
structure–function relationship in a broader sense, which is yet to be achieved. The stability, structure, aggregation and
molecular chaperone activity of α-crystallin differ significantly from species to species. These differences clearly reflect
specific structural changes of the protein, which, in turn, may contribute to the transparency and refractive power of the eye
lens. Several eye diseases, such as diabetic retinopathy involve oxidative stress, followed by a decrease in total soluble lens
proteins and a decreased amount of βB1 crystallins. Intraperitoneal injection of edaravone drugs, a member of the substituted
2-pyrazolin-5-one class, and its analogs are now being tried to revert back crystallin activity and inhibit hyperglycemia and
oxidative stress-mediated eye cell damage. In the upcoming future, edaravone-like drugs or their analogs can be synthesized
and targeted for better efficacy.
Keywords ɑ-Crystallin· Chaperone activity· Edaravone drugs· Eye diseases· Structure–function relationship·
Vertebrates
Introduction
The vertebrate eye evolved through an evolutionary sequence
involving numerous subtle changes. The eye lens is a clear
lentiform structure which acts as a refractive medium to
focus light onto the tissue layer. It varies in shape and struc-
ture, starting from totally different species, which can be an
attainable causative issue for the structural basis of the pre-
dominant crystallin proteins. For aquatic animals, the lens
is significantly thicker and nearly spherical to extend refrac-
tion, whereas in terrestrial animals, the lens of primates such
as humans is usually flat. In fish and amphibians, the lens is
spherical in form, whereas in lampreys and shags, the lens
is not hooked up to the outer surface of the eyeball. These
variations could be directly connected with the expression
of crystallins. Among proteins, crystallins are a bunch of
proteins found within the eye lens constituting nearly 90%
of its proteins. α-Crystallin consists of two subunits, αA and
αB, ranging from 300,000 to over 1,000,000 Da (Biswas
etal. 2011; Saha and Das 2004, 2015). They are known to
function similarly to molecular chaperones, i.e., preventing
the aggregation of denatured proteins in the eye lens.
Crystallin proteins exist at very high concentrations in the
lens, ranging from 400mg/mL in humans (Delaye and Tar-
dieu 1983) and higher over 1000mg/ml in some aquatic spe-
cies. The most widespread and apparently ancient crystallins
found in vertebrate lineages are of three classes, namely ,α-,
β- and γ-crystallins. The β- and γ-crystallins are not related
to α-crystallins and are highly expressed in the vertebrate
eye lens as well, with low levels of expression in different
retinal cell types. These proteins have been intensely stud-
ieddueto their primaryroles in preventing cataract. How-
ever, fewer studies have reflected on a comparison of the
α-crystallins’ structure, function or physiology. An insight
* Sudipa Saha
sudipa@sxccal.edu
1 Department ofBiotechnology, St. Xavier’s College
(Autonomous), Kolkata, India
2 Present Address: Department ofBiotechnology, St. Xavier’s
College (Autonomous), 30, Mother Teresa Sarani, Kolkata,
WestBengal700016, India
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