Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter

被引:261
作者
Karpowich, N
Martsinkevich, O
Millen, L
Yuan, YR
Dai, PL
MacVey, K
Thomas, PJ
Hunt, JF
机构
[1] Columbia Univ, Dept Biol Sci, Fairchild Ctr 702A, New York, NY 10027 USA
[2] Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75235 USA
基金
美国国家卫生研究院;
关键词
ABC transporter; ATPase; induced fit; mechanochemistry; transmembrane transport; protein crystallography;
D O I
10.1016/S0969-2126(01)00617-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: ATP binding cassette (ABC) transporters are ubiquitously distributed transmembrane solute pumps that play a causative role in numerous diseases. Previous structures have defined the fold of the ABC and established the flexibility of its alpha -helical subdomain. But the nature of the mechanical changes that occur at each step of the chemical ATPase cycle have not been defined. Results: Crystal structures were determined of the MJ1267 ABC from Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison of these structures reveals an induced-fit effect at the active site likely to be a consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop following the Walker B moves toward the Walker A (P-loop) coupled to backbone conformational changes in the intervening "H-loop", which contains an invariant histidine. These changes affect the region believed to mediate intercassette interaction in the ABC transporter complex. Comparison of the Mg-ADP-bound structure of MJ1267 to the ATP-bound structure of HisP suggests that an outward rotation of the alpha -helical subdomain is coupled to the loss of a molecular contact between the gamma -phosphate of ATP and an invariant glutamine in a segment connecting this subdomain to the core of the cassette. Conclusions: The induced-fit effect and rotation of the alpha -helical subdomain may play a role in controlling the nucleotide-dependent change in cassette-cassette interaction affinity believed to represent the power-stroke of ABC transporters. Outward rotation of the alpha -helical subdomain also likely facilitates Mg-ADP release after hydrolysis. The MJ1267 structures therefore define features of the nucleotide-dependent conformational changes that drive transmembrane transport in ABC transporters.
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收藏
页码:571 / 586
页数:16
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