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

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)93-105
Number of pages13
JournalMatrix Biology
StatePublished - Jul 26 2015

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: TRP was the recipient of a Canadian Institutes of Health Research postdoctoral fellowship and is currently supported by the Marie Skłodowska-Curie Fellowship. JS holds a Canada Research Chair in Structure Biology.

This investigation was supported in part by the Multiple Sclerosis Society of Canada and by the Canadian Institute of Health Research (RPA-109759).

ASJC Scopus subject areas

  • Molecular Biology


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