Importance of the positively charged residue at position 54 to the chaperoning function, conformational stability and amyloidogenic nature of human αA-crystallin
| Autor: | Boris I. Kurganov, Ali Niazi, Ali Akbar Moosavi-Movahedi, Ahmad Oryan, Reza Yousefi, Kazem Khoshaman |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system Arginine Protein Conformation Protein Stability Chemistry Lysine Structural integrity General Medicine alpha-Crystallin A Chain Biochemistry 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Crystallin Mutation 030221 ophthalmology & optometry Humans Missense mutation Conformational stability Molecular Biology Molecular Chaperones |
| Zdroj: | The Journal of Biochemistry. 163:187-199 |
| ISSN: | 1756-2651 0021-924X |
| Popis: | Arginine 54 (R54) in αA-Crystallin (αA-Cry) is highly conserved within different species. Recently, three missense mutations at this hot spot position have been reported to cause congenital cataract disorders. To investigate the impact of charge on structural and functional aspects of αA-Cry, R54 was individually substituted with lysine and aspartate. Replacement of R54 with the positively and negatively charged residues led to structural alteration and reduction in the protein conformational and proteolytic stability. Also, these mutations resulted in important increase in the amyloidogenic propensity of αA-Cry. Additionally, all these changes were more pronounced upon R54D mutation. Keeping the positive charge by R54K mutation, the structural integrity and stability of αA-Cry were partially preserved. Our results suggest that arginine 54 may also participate in salt bridge formation and conformational stabilization of αA-Cry. Also, it seems that unique physicochemical properties of arginine 54 may have a prominent role in the structural integrity, conformational stability and functional aspects of human αA-Cry. |
| Databáze: | OpenAIRE |
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