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Revision as of 23:37, 12 November 2020

Alpha- Crystallin AB Chain

Alpha A and Alpha B Crystallin are proteins that encoded by the genes CRYAA and CRYAB. Alpha A and B are a major protein component of the mammalian eye lens. Alpha crystallin is mainly found on the lens of the eye with trace amounts in other tissues while Alpha B is essentially considered a ubiquitous protein. ^[1]

1 Function
2 Disease
3 Relevance
4 Structural highlights

Function

This protein contributes to the transparency and refractive index of the eye lens. Alpha- Crystallin can act as chaperones preventing the aggregation of various proteins. Even though they at as molecular chaperones, they don't renature proteins and release them like true chaperones do; instead, they hold proteins in large soluble aggregates. ^[2]

Disease

Cataracts 9, multiple types

This disease is caused by mutations affecting the eye lens. One of those mutations is usually R116C where an arginine is mutated to a cysteine. R116C is generally linked to one form of autosomal congenital cataracts. Congenital cataracts refers to the opacification of the eye lens that occurs at birth while infantile cataracts refers to the opacification of eye lens that developed during the first year. ^[3] An opacification of the crystalline sense of the eye occurs, in most instances, may lead to impairment or blindness. Opacities vary in morphology it might be static or progressive. ^[4]

Myopathy, Miofibrillar

A group of chronic neuromuscular disorder characterized by the disintegration of the sarcomere Z disc and myofibrils. Myopathy is characterized by weakness of proximal and distal limbs, weakness of neck, hypertrophy cardiomyopathy, and cataracts in a subset of patients.

Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin

This is another form of myopathy myofibril, but it happens in infants. It is a chronic neuromuscular disorder characterized by disintegration of sarcomere Z disc and myofibrils. MFMFIH-CRYAB has onset on the first weeks of life after the neonatal period. Affected infants show rapid muscular rigidity of trunks and limbs which is associated with increasing respiratory difficulties resulting in death before the age of 3.

Relevance

Alpha Crystallin A 1-172 is found at nearly 2 folds higher in diabetic lenses than an aged matched control lens. In humans, the alpha A gene is found in chromosome 21 and encodes for 173 amino acid residues while the alpha B gene is found in chromosome 11 and encodes for 175 amino acids.^[1] In mammalian lens, the molar ratio between alpha A and alpha B is a 3 to 1 ratio. ^[5] An increased level of Alpha Crystallin B chain has been associated with various diseases such Alexander's disease, Alzheimer's, and Parkinson's. ^[6]

Structural highlights

This structure highlight shows where is located in the A chain. A mutation of this amino acid to cysteine will lead to cataracts. ^[1]

The following structure shows where is located. The mutation of this amino acid in the B chain of crystalline gene decreased interaction with wild-type CRYAA and CRYAB. However, it increases interactions with CRBB2 and CRYGC leading to cytoplasmic aggregation. ^[7] Also, when Arg is mutated to Gly, it causes desmin- related myopathy, cardiomyopathy, and cataracts. Also, this mutation reduces chaperone protection activity and in some target proteins promoted aggregation. ^[1]

This highlight shows the location of the involved in inter-subunit bridging of Zn ions which enhances stability.^[8] This is crucial as there is no protein turnover in the lens.

The following structure shows with all the chains that make it up.

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Horwitz J. Alpha-crystallin. Exp Eye Res. 2003 Feb;76(2):145-53. doi: 10.1016/s0014-4835(02)00278-6. PMID:12565801 doi:http://dx.doi.org/10.1016/s0014-4835(02)00278-6
↑ van Ketel WG. [Contact allergy for Alstroemeria (inca lily)]. Ned Tijdschr Geneeskd. 1990 Nov 24;134(47):2310-1. PMID:2255369
↑ Thompson J, Lakhani N. Cataracts. Prim Care. 2015 Sep;42(3):409-23. doi: 10.1016/j.pop.2015.05.012. PMID:26319346 doi:http://dx.doi.org/10.1016/j.pop.2015.05.012
↑ Cobb BA, Petrash JM. Structural and functional changes in the alpha A-crystallin R116C mutant in hereditary cataracts. Biochemistry. 2000 Dec 26;39(51):15791-8. doi: 10.1021/bi001453j. PMID:11123904 doi:http://dx.doi.org/10.1021/bi001453j
↑ Srinivas P, Narahari A, Petrash JM, Swamy MJ, Reddy GB. Importance of eye lens alpha-crystallin heteropolymer with 3:1 alphaA to alphaB ratio: stability, aggregation, and modifications. IUBMB Life. 2010 Sep;62(9):693-702. doi: 10.1002/iub.373. PMID:20836128 doi:http://dx.doi.org/10.1002/iub.373
↑ Head MW, Corbin E, Goldman JE. Overexpression and abnormal modification of the stress proteins alpha B-crystallin and HSP27 in Alexander disease. Am J Pathol. 1993 Dec;143(6):1743-53. PMID:8256860
↑ Fu L, Liang JJ. Alteration of protein-protein interactions of congenital cataract crystallin mutants. Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1155-9. PMID:12601044
↑ Karmakar S, Das KP. Identification of histidine residues involved in Zn(2+) binding to alphaA- and alphaB-crystallin by chemical modification and MALDI TOF mass spectrometry. Protein J. 2012 Oct;31(7):623-40. doi: 10.1007/s10930-012-9439-0. PMID:22890888 doi:http://dx.doi.org/10.1007/s10930-012-9439-0

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_GGC11"

@@ Line 23: / Line 23: @@
 This structure highlight shows where <scene name='78/781195/2klrarg_116/1'>Arg 116</scene> is located in the A chain. A mutation of this amino acid to cysteine will lead to cataracts. <ref name="alpha" />
-The following structure shows where <scene name='78/781195/Arginine120b/1'>Arginine 120 on B chain</scene> is located. The mutation of this amino acid in the B chain of crystalline gene decreased interaction with wild-type CRYAA and CRYAB. However, it increases interactions with CRBB2 and CRYGC leading to cytoplasmic aggregation. <ref>PMID:12601044</ref>
+The following structure shows where <scene name='78/781195/Arginine120b/2'>Arginine 120 on B chain</scene> is located. The mutation of this amino acid in the B chain of crystalline gene decreased interaction with wild-type CRYAA and CRYAB. However, it increases interactions with CRBB2 and CRYGC leading to cytoplasmic aggregation. <ref>PMID:12601044</ref> Also, when Arg is mutated to Gly, it causes desmin- related myopathy, cardiomyopathy, and cataracts. Also, this mutation reduces chaperone protection activity and in some target proteins promoted aggregation. <ref name="alpha" />
 This highlight shows the location of the <scene name='78/781195/His_abr/1'>Histidine amino acids</scene> involved in inter-subunit bridging of Zn ions which enhances stability.<ref>PMID:22890888</ref> This is crucial as there is no protein turnover in the lens.
 The following structure shows <scene name='78/781195/Crystallin/1'>Alpha Crystallin Structure</scene> with all the chains that make it up.
-This sample structure shows the amino acid <scene name='78/781195/Arg_120/1'>Arg 120</scene>. When Arg is mutated to Gly, it causes desmin related myopathy, cardiomyopathy, and cataracts. Also, this mutation reduces chaperone protection activity and in some target proteins promoted aggregation. <ref name="alpha" />
 </StructureSection>
 == References ==
 <references/>

Sandbox GGC11

From Proteopedia

Revision as of 23:37, 12 November 2020

Alpha- Crystallin AB Chain

Contents

Function

Disease

Relevance

Structural highlights

References

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