Thompson James R, Ryan Zachary C, Salisbury Jeffrey L, Kumar Rajiv
Department of Physiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
J Biol Chem. 2006 Jul 7;281(27):18746-52. doi: 10.1074/jbc.M513667200. Epub 2006 Apr 20.
Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered alpha-helical linker. A stretch of the amino-terminal domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an alpha-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin.
人中心蛋白2在中心体功能中起关键作用，并通过与着色性干皮病C组蛋白结合来刺激核苷酸切除修复。为了确定人中心蛋白2的结构，并深入了解中心蛋白与着色性干皮病C组蛋白之间的分子相互作用，我们对与着色性干皮病C组肽复合的钙负载全长中心蛋白2的晶体结构进行了表征。我们的结构表明，中心蛋白2的羧基末端结构域结合该肽和两个钙原子，而氨基末端叶处于通过有序的α-螺旋连接体远距离定位的封闭构象。中心蛋白特有的一段氨基末端结构域似乎是无序的。两个与中心蛋白2结合的着色性干皮病C组肽也相互作用形成α-螺旋卷曲螺旋。中心蛋白2与每个肽之间的界面主要是非极性的，并且已经鉴定出XPC的关键疏水残基，这使我们提出了一种新的中心蛋白结合基序。
