CRYAB

Today, CRYAB continues to be a topic of great relevance and interest to a large number of people around the world. For decades, CRYAB has been the subject of debates, research and discussions in various areas of knowledge, as well as in society in general. Its impact and significance make it a topic of constant study and reflection, which continues to generate new perspectives, discoveries and points of view. In this article, we will explore different aspects of CRYAB, its influence in various areas and its importance today.

CRYAB
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCRYAB, CMD1II, CRYA2, CTPP2, CTRCT16, HEL-S-101, HSPB5, MFM2, crystallin alpha B
External IDsOMIM: 123590; MGI: 88516; HomoloGene: 68209; GeneCards: CRYAB; OMA:CRYAB - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1410

12955

Ensembl

ENSG00000109846

ENSMUSG00000032060

UniProt

P02511

P23927

RefSeq (mRNA)

NM_001289782
NM_001289784
NM_001289785
NM_009964

RefSeq (protein)

NP_001276711
NP_001276713
NP_001276714
NP_034094

Location (UCSC)Chr 11: 111.91 – 111.92 MbChr 9: 50.66 – 50.67 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Alpha-crystallin B chain is a protein that in humans is encoded by the CRYAB gene.[5] It is part of the small heat shock protein family and functions as molecular chaperone that primarily binds misfolded proteins to prevent protein aggregation, as well as inhibit apoptosis and contribute to intracellular architecture.[6][7][8] Post-translational modifications decrease the ability to chaperone.[6][8] Mutations in CRYAB cause different cardiomyopathies,[9] skeletal myopathies[10] mainly myofibrillar myopathy,[11] and also cataracts.[12] In addition, defects in this gene/protein have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[6][7][8]

Structure

Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups.

Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. These heterogeneous aggregates consist of 30–40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively.[6]

Function

Alpha B chain crystallins (αBC) can be induced by heat shock, ischemia, and oxidation, and are members of the small heat shock protein (sHSP also known as the HSP20) family.[6][13] They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead, they bind improperly folded proteins to prevent protein aggregation.[6][7][8]

Furthermore, αBC may confer stress resistance to cells by inhibiting the processing of the pro-apoptotic protein caspase-3.[8] Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy.[6]

Clinical significance

Although not yet clearly understood, defective chaperone activity is expected to trigger the accumulation of protein aggregates and underlie the development of α-crystallinopathy, or the failure of protein quality control, resulting in protein deposition diseases such as Alzheimer’s disease and Parkinson’s disease. Mutations in CRYAB could also cause restrictive cardiomyopathy.[14] ER-anchored αBC can suppress aggregate formation mediated by the disease mutant. Thus, modulation of the micromilieu surrounding the ER membrane can serve as a potential target in developing pharmacological interventions for protein deposition disease.[7]

Though expressed highly in eye lens and muscle tissues, αBC can also be found in several types of cancer, among which head and neck squamous cell carcinoma (HNSCC) and breast carcinomas, as well as in patients with tuberous sclerosis.[15] αBC expression is associated with metastasis formation in HNSCC and in breast carcinomas and in other types of cancer, expression is often correlated with poor prognosis as well.[16] The expression of αBC can be increased during various stresses, like heat shock, osmotic stress or exposure to heavy metals, which then may lead to prolonged survival of cells under these conditions.[8]

Interactions

CRYAB has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109846 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032060 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Jeanpierre C, Austruy E, Delattre O, Jones C, Junien C (March 1993). "Subregional physical mapping of an alpha B-crystallin sequence and of a new expressed sequence D11S877E to human 11q". Mammalian Genome. 4 (2): 104–8. doi:10.1007/BF00290434. PMID 8431633. S2CID 9038111.
  6. ^ a b c d e f g "Entrez Gene: CRYAB crystallin, alpha B".
  7. ^ a b c d Yamamoto S, Yamashita A, Arakaki N, Nemoto H, Yamazaki T (December 2014). "Prevention of aberrant protein aggregation by anchoring the molecular chaperone αB-crystallin to the endoplasmic reticulum". Biochemical and Biophysical Research Communications. 455 (3–4): 241–5. doi:10.1016/j.bbrc.2014.10.151. PMID 25449278.
  8. ^ a b c d e f van de Schootbrugge C, Schults EM, Bussink J, Span PN, Grénman R, Pruijn GJ, Kaanders JH, Boelens WC (April 2014). "Effect of hypoxia on the expression of αB-crystallin in head and neck squamous cell carcinoma". BMC Cancer. 14: 252. doi:10.1186/1471-2407-14-252. PMC 3990244. PMID 24725344.
  9. ^ Brodehl, Andreas; Gaertner-Rommel, Anna; Klauke, Bärbel; Grewe, Simon Andre; Schirmer, Ilona; Peterschröder, Andreas; Faber, Lothar; Vorgerd, Matthias; Gummert, Jan (August 2017). "The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy". Human Mutation. 38 (8): 947–952. doi:10.1002/humu.23248. ISSN 1098-1004. PMID 28493373. S2CID 13942559.
  10. ^ Vicart, P.; Caron, A.; Guicheney, P.; Li, Z.; Prévost, M. C.; Faure, A.; Chateau, D.; Chapon, F.; Tomé, F. (September 1998). "A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy". Nature Genetics. 20 (1): 92–95. doi:10.1038/1765. ISSN 1061-4036. PMID 9731540. S2CID 24517435.
  11. ^ Fichna JP, Maruszak A, Żekanowski C (November 2018). "Myofibrillar myopathy in the genomic context". Journal of Applied Genetics. 59 (4): 431–439. doi:10.1007/s13353-018-0463-4. PMID 30203143.
  12. ^ Fichna JP, Potulska-Chromik A, Miszta P, Redowicz MJ, Kaminska AM, Zekanowski C, Filipek S (November 2016). "A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure". BBA Clinical. 7: 1–7. doi:10.1016/j.bbacli.2016.11.004. PMC 5124346. PMID 27904835.
  13. ^ Easterbrook M, Trope G (1989). "Value of Humphrey perimetry in the detection of early chloroquine retinopathy". Lens and Eye Toxicity Research. 6 (1–2): 255–68. PMID 2488020.
  14. ^ Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I, Peterschröder A, Faber L, Vorgerd M, Gummert J, Anselmetti D, Schulz U, Paluszkiewicz L, Milting H (August 2017). "The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy". Human Mutation. 38 (8): 947–952. doi:10.1002/humu.23248. PMID 28493373. S2CID 13942559.
  15. ^ Wang F, Chen X, Li C, Sun Q, Chen Y, Wang Y, Peng H, Liu Z, Chen R, Liu K, Yan H, Ye BH, Kwiatkowski DJ, Zhang H (August 2014). "Pivotal role of augmented αB-crystallin in tumor development induced by deficient TSC1/2 complex". Oncogene. 33 (34): 4352–8. doi:10.1038/onc.2013.401. PMID 24077282.
  16. ^ Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, Diaz LK, Turbin D, Karaca G, Wiley E, Nielsen TO, Perou CM, Cryns VL (January 2006). "AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer". The Journal of Clinical Investigation. 116 (1): 261–70. doi:10.1172/JCI25888. PMC 1323258. PMID 16395408.
  17. ^ a b c d Fu L, Liang JJ (February 2002). "Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay". The Journal of Biological Chemistry. 277 (6): 4255–60. doi:10.1074/jbc.M110027200. PMID 11700327.
  18. ^ Sugiyama Y, Suzuki A, Kishikawa M, Akutsu R, Hirose T, Waye MM, Tsui SK, Yoshida S, Ohno S (January 2000). "Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation". The Journal of Biological Chemistry. 275 (2): 1095–104. doi:10.1074/jbc.275.2.1095. PMID 10625651.
  19. ^ Kato K, Shinohara H, Goto S, Inaguma Y, Morishita R, Asano T (April 1992). "Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle". The Journal of Biological Chemistry. 267 (11): 7718–25. doi:10.1016/S0021-9258(18)42574-4. PMID 1560006.
  20. ^ Boelens WC, Croes Y, de Jong WW (January 2001). "Interaction between αB-crystallin and the human 20S proteasomal subunit C8/α7". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1544 (1–2): 311–9. doi:10.1016/S0167-4838(00)00243-0. PMID 11341940.

Further reading