Crystal Structure of Caskin1/CASK complex reveals the molecular basis of the binding specificity of CASK_CAMK domain and its binding partners
Crystal Structure of Caskin1/CASK complex reveals the molecular basis of the binding specificity of CASK_CAMK domain and its binding partners
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Caskin1/CASK复合物的晶体结构揭示了CASK_CAMK结构域及其结合伙伴的结合特异性的分子基础
DOI：
10.1101/2022.01.16.476467
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Wei Liu
中科院分区：
文献类型：
--
作者：
Yue Wang;Qiangou Chen;Riting Jiang;Xiaoyang Ye;Jun Wan;Jianchao Li;Wei Liu
CASK是突触系统中一种独特的支架蛋白。它将许多蛋白质连接到突触前或突触后区域，对突触囊泡的稳态至关重要。CASK的N端是钙/钙调素依赖性蛋白激酶（CAMK）结构域，具有多种功能，并与下游蛋白相互作用形成支架平台。Caskin 1是CASK的脑特异性接头蛋白之一。前期研究表明，CASK_CAMK结构域与Caskin 1 CID结构域的相互作用亲和力较低。在这项研究中，我们通过重新映射相互作用边界并解决其复杂结构来重新访问这种相互作用。在此基础上，我们系统地比较了CASK_CAMK与其他结合伙伴的相互作用。我们的研究结果表明，CAMK结构域通过其C端的凹槽（α1和α2之间）占据CID肽，并且在CID结构域中存在高度保守的特征基序（X-x-X-W-X-R），其中X-x是含有酸性侧链的残基，x是任何氨基酸残基，X-x是疏水残基，W是色氨酸，R是精氨酸。这些发现使我们能够鉴定CASK_CAMK的几种新的潜在细胞质结合伴侣。
CASK is a unique scaffold protein in the synapse system. It links numerous proteins to the pre- or post-synaptic region and is critical to the homeostasis of synaptic vesicles. The N-terminus of CASK is a calcium/calmodulin-dependent protein kinase (CAMK) domain, which has diverse functions and interacts with downstream proteins to form a scaffold platform. Caskin1 is one of the brain-specific adaptor proteins of CASK. Previous studies showed that CASK_CAMK domain interacts with Caskin1 CID domain with relatively low affinity. In this study, we re-visit this interaction by remapping the interaction boundary and solving their complex structure. Based on the structure, we systematically compared the interactions between CASK_CAMK and other binding partners. Our results showed that CAMK domain occupies the CID peptide by using its C-lobe groove (between the α1 and α2) and there is a highly conserved signature motif (ζ-x-ψ-W-ψ-x-R) in the CID domain, where ζ is acidic side chain containing residues, x is any amino acid residue, ψ is hydrophobic residues, W is for tryptophan, and R is arginine. These findings allowed us to identify several new potential cytoplasmic binding partners for CASK_CAMK.
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DOI：
10.1083/jcb.142.1.139
发表时间：
1998-07-13
期刊：
The Journal of cell biology
影响因子：
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作者：
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