Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction

Patel, Trushar R. and Nikodemus, Denise and Besong, Tabot M.D. and Reuten, Raphael and Meier, Markus and Harding, Stephen E. and Winzor, Donald J. and 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

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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.

Item Type: Article
Keywords: Analytical ultracentrifugation; CD spectroscopy; Dynamic light scattering; Extracellular matrix; Laminin short arms; Protein self-association; Surface plasmon resonance
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Biosciences
Identification Number: 10.1016/j.matbio.2015.06.005
Depositing User: Eprints, Support
Date Deposited: 10 May 2017 14:23
Last Modified: 10 May 2017 21:44
URI: http://eprints.nottingham.ac.uk/id/eprint/42730

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