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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

Authors

Trushar R. Patel

Denise Nikodemus

Tabot M.D. Besong

Raphael Reuten

Markus Meier

Donald J. Winzor

Manuel Koch

Jörg Stetefeld



Abstract

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.

Journal Article Type Article
Publication Date Jan 1, 2016
Journal Matrix Biology
Print ISSN 0945-053X
Electronic ISSN 1569-1802
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 49
APA6 Citation Patel, T. R., Nikodemus, D., Besong, T. M., Reuten, R., Meier, M., Harding, S. E., …Stetefeld, J. (2016). Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction. Matrix Biology, 49, doi:10.1016/j.matbio.2015.06.005
DOI https://doi.org/10.1016/j.matbio.2015.06.005
Keywords Analytical ultracentrifugation; CD spectroscopy; Dynamic light scattering; Extracellular matrix; Laminin short arms; Protein self-association; Surface plasmon resonance
Publisher URL http://www.sciencedirect.com/science/article/pii/S0945053X15001237
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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