Lorenz Sonja, Vakonakis Ioannis, Lowe Edward D, Campbell Iain D, Noble Martin E M, Hoellerer Maria K
Laboratory of Molecular Biophysics, University of Oxford, Oxford OX1 3QU, United Kingdom.
Structure. 2008 Oct 8;16(10):1521-31. doi: 10.1016/j.str.2008.08.007.
The adaptor protein paxillin contains five conserved leucine-rich (LD) motifs that interact with a variety of focal adhesion proteins, such as alpha-parvin. Here, we report the first crystal structure of the C-terminal calponin homology domain (CH(C)) of alpha-parvin at 1.05 A resolution and show that it is able to bind all the LD motifs, with some selectivity for LD1, LD2, and LD4. Cocrystal structures with these LD motifs reveal the molecular details of their interactions with a common binding site on alpha-parvin-CH(C), which is located at the rim of the canonical fold and includes part of the inter-CH domain linker. Surprisingly, this binding site can accommodate LD motifs in two antiparallel orientations. Taken together, these results reveal an unusual degree of binding degeneracy in the paxillin/alpha-parvin system that may facilitate the assembly of dynamic signaling complexes in the cell.
衔接蛋白桩蛋白含有五个保守的富含亮氨酸（LD）基序，这些基序可与多种粘着斑蛋白相互作用，如α-原肌球蛋白。在此，我们报道了α-原肌球蛋白C端钙调蛋白同源结构域（CH(C)）在1.05埃分辨率下的首个晶体结构，并表明它能够结合所有的LD基序，对LD1、LD2和LD4具有一定的选择性。与这些LD基序的共晶体结构揭示了它们与α-原肌球蛋白-CH(C)上一个共同结合位点相互作用的分子细节，该结合位点位于典型折叠的边缘，包括CH结构域间连接子的一部分。令人惊讶的是，这个结合位点可以容纳两个反平行方向的LD基序。综上所述，这些结果揭示了桩蛋白/α-原肌球蛋白系统中不同寻常程度的结合简并性，这可能有助于细胞中动态信号复合物的组装。
