Structural basis of PSGL‐1 binding to ERM proteins
Structural basis of PSGL‐1 binding to ERM proteins
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DOI：
10.1111/j.1365-2443.2007.01137.x
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发表时间：
2007-12
期刊：
影响因子：
2.1
通讯作者：
Y. Takai;K. Kitano;S. Terawaki;R. Maesaki;T. Hakoshima
中科院分区：
文献类型：
--
作者：
Y. Takai;K. Kitano;S. Terawaki;R. Maesaki;T. Hakoshima
P -选择素糖蛋白配体- 1 （PSGL - 1）是一种与O -糖基化的细胞外唾液黏附蛋白的粘附分子，参与白细胞炎症反应。激活后，ERM蛋白介导PSGL - 1在极化细胞表面的重新分配，促进与靶分子的结合。ERM蛋白识别一个短的结合基序，motif‐1，保守地存在于粘附分子的细胞质尾部，而PSGL‐1缺乏与ERM蛋白结合的重要基序‐1残基。radixin FERM结构域与PSGL‐1近膜肽之间的复合物的晶体结构表明，该肽通过形成与β -链β - 5c相结合的β -链结合FERM亚结构域C的凹槽，随后形成一个向溶剂翻转的环。由于缺少关键的Motif‐1丙氨酸残基，PSGL‐1中不存在FERM-ICAM‐2复合物中的Motif‐1 310螺旋，并且PSGL‐1减少了其与亚结构域c的接触面积。非保守位置被大残基Met9和His8占据，这稳定了肽构象并增强了凹槽结合。非守恒残基在补偿由于缺少对结合具有重要意义的守恒残基而导致的结合能损失方面起着重要的作用。
P‐selectin glycoprotein ligand‐1 (PSGL‐1), an adhesion molecule with O‐glycosylated extracellular sialomucins, is involved in leukocyte inflammatory responses. On activation, ezrin–radixin–moesin (ERM) proteins mediate the redistribution of PSGL‐1 on polarized cell surfaces to facilitate binding to target molecules. ERM proteins recognize a short binding motif, Motif‐1, conserved in cytoplasmic tails of adhesion molecules, whereas PSGL‐1 lacks Motif‐1 residues important for binding to ERM proteins. The crystal structure of the complex between the radixin FERM domain and a PSGL‐1 juxtamembrane peptide reveals that the peptide binds the groove of FERM subdomain C by forming a β‐strand associated with strand β5C, followed by a loop flipped out towards the solvent. The Motif‐1 310 helix present in the FERM–ICAM‐2 complex is absent in PSGL‐1 given the absence of a critical Motif‐1 alanine residue, and PSGL‐1 reduces its contact area with subdomain C. Non‐conserved positions are occupied by large residues Met9 and His8, which stabilize peptide conformation and enhance groove binding. Non‐conserved residues play an important role in compensating for loss of binding energy resulting from the absence of conserved residues important for binding.