Al-Bassam Jawdat, Larsen Nicholas A, Hyman Anthony A, Harrison Stephen C
Jack and Eileen Connors Laboratory of Structural Biology , Harvard Medical School, Boston, MA 02115, USA.
Structure. 2007 Mar;15(3):355-62. doi: 10.1016/j.str.2007.01.012.
Members of the XMAP215/Dis1 family of microtubule-associated proteins (MAPs) are essential for microtubule growth. MAPs in this family contain several 250 residue repeats, called TOG domains, which are thought to bind tubulin dimers and promote microtubule polymerization. We have determined the crystal structure of a single TOG domain from the Caenorhabditis elegans homolog, Zyg9, to 1.9 A resolution, and from it we describe a structural blueprint for TOG domains. These domains are flat, paddle-like structures, composed of six HEAT-repeat elements stacked side by side. The two wide faces of the paddle contain the HEAT-repeat helices, and the two narrow faces, the intra- and inter-HEAT repeat turns. Solvent-exposed residues in the intrarepeat turns are conserved, both within a particular protein and across the XMAP215/Dis1 family. Mutation of some of these residues in the TOG1 domain from the budding yeast homolog, Stu2p, shows that this face indeed participates in the tubulin contact.
微管相关蛋白(MAPs)的XMAP215/Dis1家族成员对微管生长至关重要。该家族中的MAPs包含几个250个残基的重复序列,称为TOG结构域,据认为这些结构域可结合微管蛋白二聚体并促进微管聚合。我们已确定秀丽隐杆线虫同源物Zyg9的单个TOG结构域的晶体结构,分辨率达到1.9埃,并据此描述了TOG结构域的结构蓝图。这些结构域是扁平的桨状结构,由六个HEAT重复元件并排堆叠而成。桨的两个宽面包含HEAT重复螺旋,而两个窄面包含HEAT重复序列内部和之间的转角。特定蛋白质内部以及XMAP215/Dis1家族中,重复序列内部转角处暴露于溶剂的残基是保守的。对芽殖酵母同源物Stu2p的TOG1结构域中一些此类残基进行突变后发现,该面确实参与了与微管蛋白的接触。