PUBLICATION
Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction
- Authors
- Patel, T.R., Nikodemus, D., Besong, T.M., Reuten, R., Meier, M., Harding, S.E., Winzor, D.J., Koch, M., Stetefeld, J.
- ID
- ZDB-PUB-150729-8
- Date
- 2016
- Source
- Matrix biology : journal of the International Society for Matrix Biology 49: 93-105 (Journal)
- Registered Authors
- Keywords
- Analytical ultracentrifugation, CD spectroscopy, Dynamic light scattering, Extracellular matrix, Laminin short arms, Protein self-association, Surface plasmon resonance
- MeSH Terms
-
- Binding Sites
- Dynamic Light Scattering
- Genes, Lethal*
- Humans
- Laminin/chemistry
- Laminin/genetics*
- Laminin/metabolism*
- Models, Molecular
- Mutation*
- Protein Conformation
- Protein Multimerization
- Protein Structure, Tertiary
- Surface Plasmon Resonance
- PubMed
- 26215696 Full text @ Matrix Biol.
Citation
Patel, T.R., Nikodemus, D., Besong, T.M., Reuten, R., Meier, M., Harding, S.E., Winzor, D.J., Koch, M., Stetefeld, J. (2016) Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction. Matrix biology : journal of the International Society for Matrix Biology. 49:93-105.
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-1N), α-5 (hLM α-5N) and β-3 (hLM β-3N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1N 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping