モジュラータンパク質の構造解析: 受容体構造生物学における中心課題

抄録

Extracellular proteins and receptor ectodomain fragments remain to be challenging targets for X-ray crystallography, due to the difficulties associated with the recombinant production as well as their intrinsic interdomain flexibility. We have determined crystal structures of the α_IIbβ₃ integrin headpiece fragment in complex with therapeutic antagonists. Unconventional tricks exploited during the course of the crystallization, including usage of a carbohydrate processing-deficient cell line, a“clasping”tag, extensive protease polishing, and the use of Fab fragment to rigidify the complex, are described.