A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein
Kwan, Jamie J.
Donaldson, Logan W.
KAUST DepartmentComputational Bioscience Research Center (CBRC)
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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.
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.
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.
SponsorsThis 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.
JournalCell Communication and Signaling
Is Supplemented BySmirnova, 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
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