A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein

Handle URI:
http://hdl.handle.net/10754/622078
Title:
A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein
Authors:
Smirnova, Ekaterina; Kwan, Jamie J.; Siu, Ryan; Gao, Xin ( 0000-0002-7108-3574 ) ; Zoidl, Georg; Demeler, Borries; Saridakis, Vivian; Donaldson, Logan W.
Abstract:
Background: CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions.; Results: We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size.; Conclusions: This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Smirnova E, Kwan JJ, Siu R, Gao X, Zoidl G, et al. (2016) A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein. Cell Communication and Signaling 14. Available: http://dx.doi.org/10.1186/s12964-016-0140-3.
Publisher:
Springer Nature
Journal:
Cell Communication and Signaling
Issue Date:
22-Aug-2016
DOI:
10.1186/s12964-016-0140-3
Type:
Article
ISSN:
1478-811X
Sponsors:
This work was supported by the Canadian Institutes of Health Research MOP-81250 to LWD. GZ is a Canada Research Chair in Molecular and Cellular Neuroscience. XG is supported by King Abdullah University of Science and Technology. The development of the UltraScan Science Gateway is supported by the NSF grant DAC-1339649 to BD. Supercomputer time allocations were provided through NSF grant TG-MCB070039 to BD. The Center for Analytical Ultracentrifugation of Macromolecular Assemblies at the University of Texas Health Science Center at San Antonio is supported by San Antonio Cancer Institute grant P30 CA054174.
Is Supplemented By:
Smirnova, E., Kwan, J., Siu, R., Gao, X., Zoidl, G., Borries Demeler, … Donaldson, L. (2016). A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein. Figshare. https://doi.org/10.6084/m9.figshare.c.3601367; DOI:10.6084/m9.figshare.c.3601367; HANDLE:http://hdl.handle.net/10754/624128
Additional Links:
http://biosignaling.biomedcentral.com/articles/10.1186/s12964-016-0140-3
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorSmirnova, Ekaterinaen
dc.contributor.authorKwan, Jamie J.en
dc.contributor.authorSiu, Ryanen
dc.contributor.authorGao, Xinen
dc.contributor.authorZoidl, Georgen
dc.contributor.authorDemeler, Borriesen
dc.contributor.authorSaridakis, Vivianen
dc.contributor.authorDonaldson, Logan W.en
dc.date.accessioned2016-12-29T13:20:19Z-
dc.date.available2016-12-29T13:20:19Z-
dc.date.issued2016-08-22en
dc.identifier.citationSmirnova E, Kwan JJ, Siu R, Gao X, Zoidl G, et al. (2016) A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein. Cell Communication and Signaling 14. Available: http://dx.doi.org/10.1186/s12964-016-0140-3.en
dc.identifier.issn1478-811Xen
dc.identifier.doi10.1186/s12964-016-0140-3en
dc.identifier.urihttp://hdl.handle.net/10754/622078-
dc.description.abstractBackground: CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions.en
dc.description.abstractResults: We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size.en
dc.description.abstractConclusions: This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses.en
dc.description.sponsorshipThis work was supported by the Canadian Institutes of Health Research MOP-81250 to LWD. GZ is a Canada Research Chair in Molecular and Cellular Neuroscience. XG is supported by King Abdullah University of Science and Technology. The development of the UltraScan Science Gateway is supported by the NSF grant DAC-1339649 to BD. Supercomputer time allocations were provided through NSF grant TG-MCB070039 to BD. The Center for Analytical Ultracentrifugation of Macromolecular Assemblies at the University of Texas Health Science Center at San Antonio is supported by San Antonio Cancer Institute grant P30 CA054174.en
dc.publisherSpringer Natureen
dc.relation.urlhttp://biosignaling.biomedcentral.com/articles/10.1186/s12964-016-0140-3en
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAnalytical ultracentrifugationen
dc.subjectCell signalingen
dc.subjectCrystal structureen
dc.subjectNeuroscienceen
dc.subjectNuclear magnetic resonanceen
dc.subjectProtein structureen
dc.subjectScaffold proteinen
dc.titleA new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding proteinen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalCell Communication and Signalingen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Biology, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canadaen
dc.contributor.institutionDepartment of Psychology, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canadaen
dc.contributor.institutionDepartment of Biochemistry, University of Texas Health Science Center at San Antonio, 7760 Floyd Curl Drive, San Antonio, TX, 78229-3900, United Statesen
kaust.authorGao, Xinen
dc.relation.isSupplementedBySmirnova, E., Kwan, J., Siu, R., Gao, X., Zoidl, G., Borries Demeler, … Donaldson, L. (2016). A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein. Figshare. https://doi.org/10.6084/m9.figshare.c.3601367en
dc.relation.isSupplementedByDOI:10.6084/m9.figshare.c.3601367en
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624128en
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