Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin

Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin Publisher

Rezaei Somee L¹ ; Ebrahimi P² ; Agnetti G³ ; Upadhyay M⁴ ; Shobhawat R⁴ ; Kumar A⁴ ; Shahsavani MB⁵ ; Zarei I⁶ ; Amanlou M⁶ ; Saboury AA² ; Moosavimovahedi AA² ; Yousefi R¹

Show Affiliations

1. Protein Chemistry Laboratory (PCL), Institute of Biochemistry and Biophysics (IBB), University of Tehran, Iran
2. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Iran
3. Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
4. Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, India
5. Department of Biology, Shiraz University, Iran
6. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran

Source: FEBS Letters Published:2025

Abstract

αB-crystallin, a small heat shock protein, is crucial for maintaining lenticular transparency and prevents protein aggregation as a molecular chaperone in various tissues. Mutations in αB-crystallin can lead to diseases such as cataracts, cardiomyopathy, and neurodegenerative disorders. This study explores the effects of the p.R157C mutation in the C-terminal domain, near the IXI motif, which is associated with cardiomyopathy. The mutant protein was generated through site-directed mutagenesis, expressed in bacterial systems, and purified by ion-exchange chromatography. Biophysical and computational techniques revealed significant alterations in secondary structure, oligomerization, and conformational stability. The mutation also enhanced chaperone activity and promoted amyloid fibril formation. These alterations may disrupt the interactions of the p.R157C mutant αB-crystallin with cardiac proteins such as desmin and calcineurin, potentially contributing to cardiomyopathy. These findings offer mechanistic insights into αB-crystallin-related cardiomyopathy, shedding light on its pathological role and potential therapeutic targets. © 2025 Federation of European Biochemical Societies.

2. Structural Characterization and Functional Analysis of Human Αb-Crystallin With the P.R11g Mutation: Insights Into Cataractogenesis and Cardiomyopathy, International Journal of Biological Macromolecules (2025)

3. The P.K90n Mutation in Human Hspb5 Highlights the Critical Role of Lysine 90 in Chaperone Function and Structural Integrity, Archives of Biochemistry and Biophysics (2025)

4. Unraveling the Impact of the P.R107l Mutation on the Structure and Function of Human Αb-Crystallin: Implications for Cataract Formation, Biochimie (2024)

Experts (# of related papers)

Massoud Amanlou (3)

Style	Citing Format
MLA	Rezaei Somee L, et al.. "Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin." FEBS Letters, vol. , no. , 2025, pp. -.
APA	Rezaei Somee L, Ebrahimi P, Agnetti G, Upadhyay M, Shobhawat R, Kumar A, Shahsavani MB, Zarei I, Amanlou M, Saboury AA, Moosavimovahedi AA, Yousefi R (2025). Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin. FEBS Letters, (), -.
Chicago	Rezaei Somee L, Ebrahimi P, Agnetti G, Upadhyay M, Shobhawat R, Kumar A, Shahsavani MB, et al.. "Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin." FEBS Letters , no. (2025): -.
Harvard	Rezaei Somee L et al. (2025) 'Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin', FEBS Letters, (), pp. -.
Vancouver	Rezaei Somee L, Ebrahimi P, Agnetti G, Upadhyay M, Shobhawat R, Kumar A, et al.. Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin. FEBS Letters. 2025;():-.
BibTex	@article{ author = {Rezaei Somee L and Ebrahimi P and Agnetti G and Upadhyay M and Shobhawat R and Kumar A and Shahsavani MB and Zarei I and Amanlou M and Saboury AA and Moosavimovahedi AA and Yousefi R}, title = {Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin}, journal = {FEBS Letters}, volume = {}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Rezaei Somee L AU - Ebrahimi P AU - Agnetti G AU - Upadhyay M AU - Shobhawat R AU - Kumar A AU - Shahsavani MB AU - Zarei I AU - Amanlou M AU - Saboury AA AU - Moosavimovahedi AA AU - Yousefi R TI - Structural and Functional Consequences of the Cardiomyopathy-Associated P.R157c Mutation in the C-Terminal Palindromic Motif of Human Αb-Crystallin JO - FEBS Letters VL - IS - SP - EP - PY - 2025 ER -

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