期刊
CELL COMMUNICATION AND SIGNALING
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12964-016-0140-3
关键词
Analytical ultracentrifugation; Cell signaling; Crystal structure; Neuroscience; Nuclear magnetic resonance; Protein structure; Scaffold protein
类别
资金
- Canadian Institutes of Health Research [MOP-81250]
- Canada Research Chair in Molecular and Cellular Neuroscience
- King Abdullah University of Science and Technology
- NSF [DAC-1339649, TG-MCB070039]
- San Antonio Cancer Institute [P30 CA054174]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据