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

Handle URI:
http://hdl.handle.net/10754/575931
Title:
Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction
Authors:
Patel, Trushar R. ( 0000-0003-0627-2923 ) ; Nikodemus, Denise; Besong, Tabot M.D. ( 0000-0002-3572-1428 ) ; Reuten, Raphael; Meier, Markus; Harding, Stephen E.; Winzor, Donald J.; Koch, Manuel; Stetefeld, Jörg
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.
KAUST Department:
Functional Nanomaterials Lab (FuNL)
Citation:
Patel TR, Nikodemus D, Besong TMD, Reuten R, Meier M, et al. (2015) Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction. Matrix Biology. Available: http://dx.doi.org/10.1016/j.matbio.2015.06.005.
Publisher:
Elsevier BV
Journal:
Matrix Biology
Issue Date:
26-Jul-2015
DOI:
10.1016/j.matbio.2015.06.005
Type:
Article
ISSN:
0945053X
Sponsors:
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).
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0945053X15001237
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorPatel, Trushar R.en
dc.contributor.authorNikodemus, Deniseen
dc.contributor.authorBesong, Tabot M.D.en
dc.contributor.authorReuten, Raphaelen
dc.contributor.authorMeier, Markusen
dc.contributor.authorHarding, Stephen E.en
dc.contributor.authorWinzor, Donald J.en
dc.contributor.authorKoch, Manuelen
dc.contributor.authorStetefeld, Jörgen
dc.date.accessioned2015-08-25T13:19:59Zen
dc.date.available2015-08-25T13:19:59Zen
dc.date.issued2015-07-26en
dc.identifier.citationPatel TR, Nikodemus D, Besong TMD, Reuten R, Meier M, et al. (2015) Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction. Matrix Biology. Available: http://dx.doi.org/10.1016/j.matbio.2015.06.005.en
dc.identifier.issn0945053Xen
dc.identifier.doi10.1016/j.matbio.2015.06.005en
dc.identifier.urihttp://hdl.handle.net/10754/575931en
dc.description.abstractLaminins 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.en
dc.description.sponsorshipTRP 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).en
dc.language.isoenen
dc.publisherElsevier BVen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0945053X15001237en
dc.rightsArchived with thanks to Matrix Biologyen
dc.subjectAnalytical ultracentrifugationen
dc.subjectCD spectroscopyen
dc.subjectDynamic light scatteringen
dc.subjectExtracellular matrixen
dc.subjectLaminin short armsen
dc.subjectProtein self-associationen
dc.subjectSurface plasmon resonanceen
dc.titleBiophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interactionen
dc.typeArticleen
dc.contributor.departmentFunctional Nanomaterials Lab (FuNL)en
dc.identifier.journalMatrix Biologyen
dc.eprint.versionPost-printen
dc.contributor.institutionDepartment of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba R3T 2N2, Canadaen
dc.contributor.institutionSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdomen
dc.contributor.institutionInstitute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, Medical Faculty, University of Cologne, Cologne 50931, Germanyen
dc.contributor.institutionNational Center for Macromolecular Hydrodynamics, University of Nottingham, Sutton Bonington LE12 5RD, United Kingdomen
dc.contributor.institutionSchool of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australiaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorBesong, Tabot M.D.en
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