Tesmer John J G, Nance Mark R, Singh Puja, Lee Harie
Life Sciences Institute and the Department of Pharmacology, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Jun 1;68(Pt 6):622-5. doi: 10.1107/S1744309112017435. Epub 2012 May 22.
G protein-coupled receptor kinase 1 (GRK1 or rhodopsin kinase) phosphorylates activated rhodopsin and initiates a cascade of events that results in the termination of phototransduction by the receptor. Although GRK1 seems to be a monomer in solution, seven prior crystal structures of GRK1 revealed a similar domain-swapped dimer interface involving the C-terminus of the enzyme. The influence of this interface on the overall conformation of GRK1 is not known. To address this question, the crystalline dimer interface was disrupted with a L166K mutation and the structure of GRK1-L166K was determined in complex with Mg(2+) · ATP to 2.5 Å resolution. GRK1-L166K crystallized in a novel space group as a monomer and exhibited little overall conformational difference from prior structures of GRK1, although the C-terminal domain-swapped region had reorganized owing to loss of the dimer interface.
G蛋白偶联受体激酶1（GRK1或视紫红质激酶）使活化的视紫红质磷酸化，并引发一系列事件，导致该受体的光转导终止。尽管GRK1在溶液中似乎是单体，但之前的七个GRK1晶体结构揭示了一个类似的结构域交换二聚体界面，该界面涉及酶的C末端。这个界面对GRK1整体构象的影响尚不清楚。为了解决这个问题，通过L166K突变破坏了晶体二聚体界面，并确定了与Mg(2+)·ATP形成复合物的GRK1-L166K的结构，分辨率达到2.5 Å。GRK1-L166K以单体形式在一个新的空间群中结晶，与之前GRK1的结构相比，整体构象差异不大，尽管由于二聚体界面的丧失，C末端结构域交换区域发生了重组。
