A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein
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Type
ArticleAuthors
Smirnova, EkaterinaKwan, Jamie J.
Siu, Ryan
Gao, Xin

Zoidl, Georg
Demeler, Borries
Saridakis, Vivian
Donaldson, Logan W.
KAUST Department
Computational Bioscience Research Center (CBRC)Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Date
2016-08-22Online Publication Date
2016-08-22Print Publication Date
2016-12Permanent link to this record
http://hdl.handle.net/10754/622078
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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.
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.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.Publisher
Springer NatureJournal
Cell Communication and SignalingPubMed ID
27549312Relations
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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: 10754/624128
ae974a485f413a2113503eed53cd6c53
10.1186/s12964-016-0140-3
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