1g6h
From Proteopedia
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CRYSTAL STRUCTURE OF THE ADP CONFORMATION OF MJ1267, AN ATP-BINDING CASSETTE OF AN ABC TRANSPORTER
Overview
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.
About this Structure
1G6H is a Single protein structure of sequence from Methanocaldococcus jannaschii with MG, MMC and ADP as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter., Karpowich N, Martsinkevich O, Millen L, Yuan YR, Dai PL, MacVey K, Thomas PJ, Hunt JF, Structure. 2001 Jul 3;9(7):571-86. PMID:11470432
Page seeded by OCA on Tue Nov 20 15:45:15 2007
