Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction
Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. U...
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/42730/ |
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| author | Patel, Trushar R. Nikodemus, Denise Besong, Tabot M.D. Reuten, Raphael Meier, Markus Harding, Stephen E. Winzor, Donald J. Koch, Manuel Stetefeld, Jörg |
| author_facet | Patel, Trushar R. Nikodemus, Denise Besong, Tabot M.D. Reuten, Raphael Meier, Markus Harding, Stephen E. Winzor, Donald J. Koch, Manuel Stetefeld, Jörg |
| author_sort | Patel, Trushar R. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function. |
| first_indexed | 2025-11-14T19:49:50Z |
| format | Article |
| id | nottingham-42730 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:49:50Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-427302020-05-04T20:04:43Z https://eprints.nottingham.ac.uk/42730/ Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction Patel, Trushar R. Nikodemus, Denise Besong, Tabot M.D. Reuten, Raphael Meier, Markus Harding, Stephen E. Winzor, Donald J. Koch, Manuel Stetefeld, Jörg Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function. Elsevier 2016-01 Article PeerReviewed Patel, Trushar R., Nikodemus, Denise, Besong, Tabot M.D., Reuten, Raphael, Meier, Markus, Harding, Stephen E., Winzor, Donald J., Koch, Manuel and Stetefeld, Jörg (2016) Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction. Matrix Biology, 49 . pp. 93-105. ISSN 1569-1802 Analytical ultracentrifugation; CD spectroscopy; Dynamic light scattering; Extracellular matrix; Laminin short arms; Protein self-association; Surface plasmon resonance http://www.sciencedirect.com/science/article/pii/S0945053X15001237 doi:10.1016/j.matbio.2015.06.005 doi:10.1016/j.matbio.2015.06.005 |
| spellingShingle | Analytical ultracentrifugation; CD spectroscopy; Dynamic light scattering; Extracellular matrix; Laminin short arms; Protein self-association; Surface plasmon resonance Patel, Trushar R. Nikodemus, Denise Besong, Tabot M.D. Reuten, Raphael Meier, Markus Harding, Stephen E. Winzor, Donald J. Koch, Manuel Stetefeld, Jörg Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| title | Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| title_full | Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| title_fullStr | Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| title_full_unstemmed | Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| title_short | Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| title_sort | biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction |
| topic | Analytical ultracentrifugation; CD spectroscopy; Dynamic light scattering; Extracellular matrix; Laminin short arms; Protein self-association; Surface plasmon resonance |
| url | https://eprints.nottingham.ac.uk/42730/ https://eprints.nottingham.ac.uk/42730/ https://eprints.nottingham.ac.uk/42730/ |