Smith Paul C, Karpowich Nathan, Millen Linda, Moody Jonathan E, Rosen Jane, Thomas Philip J, Hunt John F
Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, New York 10027, USA.
Mol Cell. 2002 Jul;10(1):139-49. doi: 10.1016/s1097-2765(02)00576-2.
It has been proposed that the reaction cycle of ATP binding cassette (ABC) transporters is driven by dimerization of their ABC motor domains upon binding ATP at their mutual interface. However, no such ATP sandwich complex has been observed for an ABC from an ABC transporter. In this paper, we report the crystal structure of a stable dimer formed by the E171Q mutant of the MJ0796 ABC, which is hydrolytically inactive due to mutation of the catalytic base. The structure shows a symmetrical dimer in which two ATP molecules are each sandwiched between the Walker A motif in one subunit and the LSGGQ signature motif in the other subunit. These results establish the stereochemical basis of the power stroke of ABC transporter pumps.
有人提出,ATP结合盒(ABC)转运蛋白的反应循环是由其ABC运动结构域在相互界面结合ATP时的二聚化驱动的。然而,尚未观察到ABC转运蛋白中的ABC形成这样的ATP夹心复合物。在本文中,我们报道了由MJ0796 ABC的E171Q突变体形成的稳定二聚体的晶体结构,该突变体由于催化碱基的突变而水解失活。该结构显示出一个对称的二聚体,其中两个ATP分子分别夹在一个亚基中的沃克A基序和另一个亚基中的LSGGQ特征基序之间。这些结果确立了ABC转运蛋白泵动力冲程的立体化学基础。