Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner
Protein aggregation and misfolding are some of the most challenging obstacles, customarily studied for their association with amyloid pathologies. The mechanism of amyloid fibrillation development is a dynamic phenomenon involving various factors such as the intrinsic properties of protein and the p...
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MDPI AG
2021-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/3/414 |
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| author | Sania Bashir Ishfaq Ahmad Ahanger Anas Shamsi Mohamed F. Alajmi Afzal Hussain Hani Choudhry Faizan Ahmad Md. Imtaiyaz Hassan Asimul Islam |
| author_facet | Sania Bashir Ishfaq Ahmad Ahanger Anas Shamsi Mohamed F. Alajmi Afzal Hussain Hani Choudhry Faizan Ahmad Md. Imtaiyaz Hassan Asimul Islam |
| author_sort | Sania Bashir |
| collection | DOAJ |
| description | Protein aggregation and misfolding are some of the most challenging obstacles, customarily studied for their association with amyloid pathologies. The mechanism of amyloid fibrillation development is a dynamic phenomenon involving various factors such as the intrinsic properties of protein and the physical and chemical environmental conditions. The purpose of this study was to see the thermal aggregation profile of alpha-lactalbumin (α-LA) and to delineate the effect of trehalose on its aggregation profile. α-LA was subjected to thermal aggregation at high concentrations. UV-Vis spectroscopy, a turbidity assay, intrinsic fluorescence, Rayleigh scattering and a thioflavin T (ThT) assay explained the steady outcomes that 1 M trehalose repressed α-LA aggregation in the most effective way followed by 0.75 M and 0.5 M and to a significantly lesser degree by 0.25 M. Multi spectroscopic obser Sania <b>Bashir</b> ations were further entrenched by microscopy. Transmission electron microscopy confirmed that in the presence of its higher concentration, trehalose hinders fibril development in α-LA. In vitro studies were further validated by in silico studies. Molecular docking analysis indicated that trehalose occupied the binding pocket cavity of α-LA and offered several significant interactions, including H-bonds with important residues. This study provides a platform for trehalose in the therapeutic management of protein aggregation-related diseases. |
| first_indexed | 2024-03-10T13:21:04Z |
| format | Article |
| id | doaj.art-2e3a9cdf02d94905bb16d8b0fea5a03f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T13:21:04Z |
| publishDate | 2021-03-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2e3a9cdf02d94905bb16d8b0fea5a03f2023-11-21T10:00:11ZengMDPI AGBiomolecules2218-273X2021-03-0111341410.3390/biom11030414Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent MannerSania Bashir0Ishfaq Ahmad Ahanger1Anas Shamsi2Mohamed F. Alajmi3Afzal Hussain4Hani Choudhry5Faizan Ahmad6Md. Imtaiyaz Hassan7Asimul Islam8Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaProtein aggregation and misfolding are some of the most challenging obstacles, customarily studied for their association with amyloid pathologies. The mechanism of amyloid fibrillation development is a dynamic phenomenon involving various factors such as the intrinsic properties of protein and the physical and chemical environmental conditions. The purpose of this study was to see the thermal aggregation profile of alpha-lactalbumin (α-LA) and to delineate the effect of trehalose on its aggregation profile. α-LA was subjected to thermal aggregation at high concentrations. UV-Vis spectroscopy, a turbidity assay, intrinsic fluorescence, Rayleigh scattering and a thioflavin T (ThT) assay explained the steady outcomes that 1 M trehalose repressed α-LA aggregation in the most effective way followed by 0.75 M and 0.5 M and to a significantly lesser degree by 0.25 M. Multi spectroscopic obser Sania <b>Bashir</b> ations were further entrenched by microscopy. Transmission electron microscopy confirmed that in the presence of its higher concentration, trehalose hinders fibril development in α-LA. In vitro studies were further validated by in silico studies. Molecular docking analysis indicated that trehalose occupied the binding pocket cavity of α-LA and offered several significant interactions, including H-bonds with important residues. This study provides a platform for trehalose in the therapeutic management of protein aggregation-related diseases.https://www.mdpi.com/2218-273X/11/3/414protein aggregationtrehalosespectroscopytransmission electron microscopymolecular docking |
| spellingShingle | Sania Bashir Ishfaq Ahmad Ahanger Anas Shamsi Mohamed F. Alajmi Afzal Hussain Hani Choudhry Faizan Ahmad Md. Imtaiyaz Hassan Asimul Islam Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner Biomolecules protein aggregation trehalose spectroscopy transmission electron microscopy molecular docking |
| title | Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner |
| title_full | Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner |
| title_fullStr | Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner |
| title_full_unstemmed | Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner |
| title_short | Trehalose Restrains the Fibril Load towards α-Lactalbumin Aggregation and Halts Fibrillation in a Concentration-Dependent Manner |
| title_sort | trehalose restrains the fibril load towards α lactalbumin aggregation and halts fibrillation in a concentration dependent manner |
| topic | protein aggregation trehalose spectroscopy transmission electron microscopy molecular docking |
| url | https://www.mdpi.com/2218-273X/11/3/414 |
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