Biochemical characterization of G64W mutant of acidic beta-crystallin 4

Li, Wenqian; Ji, Qingshan; Wei, Zhongjie; Chen, Yulei; Zhang, Zhiyong; Yin, Xueying; Aghmiuni, Samaneh Khodi; Liu, Muziying; Chen, Weirong; Shi, Lei; Chen, Quan; Du, Xin-zheng; Yu, Li; Cao, Min‐Jie; Wang, Zhulou; Huang, Shaohui; Jin, Tengchuan; Wang, Qiwei

doi:10.1016/j.exer.2019.107712

Cited by 6 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein structure modeling showed that the substitution from a hydrophobic nonpolar Methionine (M) to hydrophilic polar Lysine (K) was predicted to reduce the hydrophobicity in the corresponding region and alter the secondary structure of the CRYBA4 protein, as a result, the mutant structure would be unstable and protein folding would consequently be impaired, most probably leading to protein aggregation. One previously reported mutation p.G64W in Greek Key II motif of CRYBA4 has been studied which led to protein misfolding, decreased stability, and blocked interaction with CRYBB1, consequently resulting in disturbance of lens transparency (Li et al, 2019). We also speculated that each of the above effects is expected to involve in the pathogenesis of p.M14K mutation.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of six β‐crystallin gene mutations associated with congenital cataract in Chinese families

Qiao

et al. 2021

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background This study aims to identify the underlying genetic defects of β‐crystallin (CRYB) genes responsible for congenital cataracts in a group of Chinese families. Methods Detailed family history and clinical data of six Chinese families with autosomal dominant congenital cataracts were recorded. Targeted exome sequencing was applied to detect the underlying genetic defects for the families. Generated variants were confirmed by PCR and sanger sequencing. Afterward, bioinformatic analysis through several computational predictive programs was performed to assess impacts of mutations on protein structure and function. Results A total of 53 participants (23 affected and 30 unaffected) from six unrelated Chinese families were recruited. Cataract phenotypes covered nuclear, total, posterior polar, pulverulent, snowflake‐like, and zonular. Through targeted exome sequencing, six mutations in four β‐crystallin genes were revealed which included five missense mutations CRYBB1 p.Q70P, CRYBB2 p.E23Q, CRYBB2 p.A49V, CRYBB2 R188C, CRYBA4 p.M14K and one splice mutation CRYBB3 c.75+1 G>A. In silico results predicted pathogenic for all four missense variants except variant CRYBB2‐p.A49V yielded results as tolerant. The CRYBB3 c.75+1 G>A splice site mutation was predicted to be deleterious by leading to a broken splice site, a premature stop codon, and subsequently resulting in a short peptide of 113 amino acids, which may affect protein features. Conclusion The obtained results expanded mutational and phenotype spectrum of β‐crystallin genes and offer clues for pathogenesis of congenital cataracts. The data also demonstrated that targeted exome sequencing is valuable for providing molecular diagnostic information for congenital cataract patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification and characterization of six β‐crystallin gene mutations associated with congenital cataract in Chinese families

Qiao

et al. 2021

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Therefore, HβA4-G64W is likely unable to bind to HβB1, thus suggesting a role for G64 in heterodimerization. [131] HβB2-R188H was unable to stabilize HβA3 like WT, suggesting this mutation also affects the heterodimer formation. In contrast to the monomeric γcrystallins, β-crystallin functionality is not a simple function of individual protein solubility and stability: these proteins must be considered in the context of the chemical milieu of the lens.…”

Section: Cataract-related Mutations In Structural Crystallins Often Imentioning

confidence: 99%

“…This mutation caused an increase in aggregation that was not ameliorated by coexpression with HβB1. Therefore, HβA4‐G64W is likely unable to bind to HβB1, thus suggesting a role for G64 in heterodimerization [131] . HβB2‐R188H was unable to stabilize HβA3 like WT, suggesting this mutation also affects the heterodimer formation.…”

Section: Cataract‐related Mutations In Structural Crystallins Often Increase Aggregation Propensitymentioning

confidence: 99%

Chemical Properties Determine Solubility and Stability in βγ‐Crystallins of the Eye Lens

et al. 2021

View full text Add to dashboard Cite

βγ-Crystallins are the primary structural and refractive proteins found in the vertebrate eye lens. Because crystallins are not replaced after early eye development, their solubility and stability must be maintained for a lifetime, which is even more remarkable given the high protein concentration in the lens. Aggregation of crystallins caused by mutations or post-translational modifications can reduce crystallin protein stability and alter intermolecular interactions. Common post-translational modifications that can cause age-related cataracts include deamidation, oxidation, and tryptophan derivatization. Metal ion binding can also trigger reduced crystallin solubility through a variety of mechanisms. Interprotein interactions are critical to maintaining lens transparency: crystallins can undergo domain swapping, disulfide bonding, and liquid-liquid phase separation, all of which can cause opacity depending on the context. Important experimental techniques for assessing crystallin conformation in the absence of a high-resolution structure include dye-binding assays, circular dichroism, fluorescence, light scattering, and transition metal FRET.

show abstract

“…Nevertheless, mtDNA depletion is mainly detected in the liver tissues and not in lung tissue. (37) Billingsley et al (38) reported for the rst time that mutations in CRYBA4 are linked to cataract and microphthalmia, (39) and the interaction of CRYBA4 with CRYBB1 is instrumental to the pathogenesis of congenital cataract. JAKMIP3 or Janus kinase and microtubule interacting protein 3 is prognostically relevant in lung cancer, although the exact mechanism has not been clari ed.…”

Section: Discussionmentioning

confidence: 99%

Saorilao-4 decoction alters the miRNA regulatory network in pulmonary fibrosis

Song

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective: To explore the effect of Mongolian medicine Saorilao-4 (SRL-4) decoction on the conserved and specific miRNAs and target genes of the gene regulatory network (GRN) involved in pulmonary fibrosis. Method: Healthy adult male SPF SD rats were randomly allocated into 4 groups. Total RNA was isolated and extracted from the lung tissues for transcriptome sequencing. The differentially expressed miRNAs (DEMs) between the different groups were screened using the difference analysis software DESeq2, and the prediction of their target genes were carried out using miRanda. Gene Ontology (GO) as well as Kyoto Encyclopedia of genes and genomes (KEGG) analyses were conducted to identify the biological functions of the target genes. Results: There were 16 DEMs in the IPF model group, whereas SRL-4 treatment resulted in 10 DEMs relative to the untreated model group. GO analysis showed that the target genes of DEMs inSRL-4 groups were enriched in 52 GO items. In addition, KEGG analysis showed that these target genes were enriched in 182 signaling pathways, and the largest number of genes were related to purine metabolism pathway. Conclusion: The progression of pulmonary fibrosis and SRL-4 anti-pulmonary fibrosis are significantly impacted by miR-433-3p, novel 202, and miR-150-3p.

show abstract

Biochemical characterization of G64W mutant of acidic beta-crystallin 4

Cited by 6 publications

References 40 publications

Identification and characterization of six β‐crystallin gene mutations associated with congenital cataract in Chinese families

Identification and characterization of six β‐crystallin gene mutations associated with congenital cataract in Chinese families

Chemical Properties Determine Solubility and Stability in βγ‐Crystallins of the Eye Lens

Saorilao-4 decoction alters the miRNA regulatory network in pulmonary fibrosis

Contact Info

Product

Resources

About