Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its binding to ERM proteins.
Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its binding to ERM proteins.
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DOI：
10.1016/j.jmb.2008.05.085
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发表时间：
2008-09
影响因子：
5.6
通讯作者：
Y. Takai;K. Kitano;S. Terawaki;R. Maesaki;T. Hakoshima
中科院分区：
文献类型：
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作者：
Y. Takai;K. Kitano;S. Terawaki;R. Maesaki;T. Hakoshima
CD 43/leukosialin/sialophorin是大多数造血细胞中的主要粘附分子，属于唾液粘蛋白超家族。在白细胞迁移和活化中，从免疫突触中排除CD 43是一个重要步骤。虽然排除需要结合的细胞质区域的ERM（ezrin/radixin/膜突蛋白）蛋白，CD 43和ERM蛋白之间的相互作用的详细的具体性质是模糊的。我们的特点是由124个氨基酸残基组成的CD 43细胞质区域的构象特性，通过流体动力学和光谱测量。超离心的沉降平衡和速度研究表明，CD 43细胞质肽在溶液中以单体和延伸形式存在。根毒素FERM（4.1和ERM）结构域和CD 43质膜区肽之间的复合物的晶体结构揭示了肽的非极性区结合FERM结构域的亚结构域C。CD 43缺乏FERM-细胞间粘附分子-2复合物中发现的FERM结合的基序-1序列，但具有两个保守的亮氨酸残基，其停靠在亚结构域C的疏水口袋中而不形成310-螺旋。CD 43上的FERM结合位点与功能性核定位信号序列重叠。我们的结构表明，调节ERM结合可能与调节膜内蛋白水解的CD 43细胞质肽的核转移。
CD43/leukosialin/sialophorin is the major adhesion molecule in most hematopoietic cells and belongs to the sialomucin superfamily. In leukocyte emigration and activation, the exclusion of CD43 from the immunological synapse is an essential step. While the exclusion requires binding of the cytoplasmic region to ERM (ezrin/radixin/moesin) proteins, the detailed specific nature of the interaction between CD43 and ERM proteins is obscure. We have characterized the conformational properties of the CD43 cytoplasmic region, consisting of 124 amino acid residues, by hydrodynamic and spectroscopic measurements. Sedimentation equilibrium and velocity studies of ultracentrifugation revealed that the CD43 cytoplasmic peptide exists in a monomeric and extended form in solution. The crystal structure of the complex between the radixin FERM (4.1 and ERM) domain and the CD43 juxtamembrane region peptide reveals that the nonpolar region of the peptide binds subdomain C of the FERM domain. CD43 lacks the Motif-1 sequence for FERM binding found in the FERM–intercellular adhesion molecule-2 complex but possesses two conserved leucine residues that dock into the hydrophobic pocket of subdomain C without forming a 310-helix. The FERM-binding site on CD43 is overlapped with the functional nuclear localization signal sequence. Our structure suggests that regulation of ERM binding may be coupled with regulated intramembrane proteolysis of CD43 followed by the nuclear transfer of the cytoplasmic peptide.