PDBsum entry 1gaj

Transport protein

PDB id: 1gaj

Contents

Protein chain

253 a.a. *

Ligands

SO4

TBU ×3

PEG-PEG

Metals

_CL ×2

Waters ×133

* Residue conservation analysis

PDB id:

1gaj

Name:

Transport protein

Title:

Crystal structure of a nucleotide-free atp-binding cassette from an abc transporter

Structure:

High-affinity branched chain amino acid transport atp- binding protein. Chain: a. Synonym: braf. Engineered: yes

Source:

Methanocaldococcus jannaschii. Organism_taxid: 2190. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

24mer (from PQS)

Resolution:

2.50Å R-factor: 0.205 R-free: 0.243

Authors:

N.Karpowich,Y.-R.Yuan,P.L.Dai,O.Martsinkevich,L.Millen,P.J.Thomas, J.F.Hunt

Key ref:

N.Karpowich et al. (2001). Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure, 9, 571-586. PubMed id: 11470432 DOI: 10.1016/S0969-2126(01)00617-7

Date:

30-Nov-00 Release date: 18-Jul-01

Protein chain

Q58663  (LIVG_METJA) -  Probable branched-chain amino acid transport ATP-binding protein LivG from Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)

Seq: 257 a.a.

Struc: 253 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/S0969-2126(01)00617-7

Structure 9:571-586 (2001)

PubMed id: 11470432

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

N.Karpowich, O.Martsinkevich, L.Millen, Y.R.Yuan, P.L.Dai, K.MacVey, P.J.Thomas, J.F.Hunt.

ABSTRACT

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.

Selected figure(s)

Figure 4.
Figure 4. Cooperative Structural Interactions Involving Phylogenetically Conserved Residues Stabilize Limiting Conformations of the g-Phosphate LinkerH bonds in the g-phosphate linker region identified based on having a heteroatom separation =< 3.4 Å are represented by dotted orange lines in the stereo pairs [57 and 58] showing:(a) The ATP-bound structure of HisP [16].(b) The Mg-ADP-bound structure of MJ0796 [21].(c) The Mg-ADP-bound structure of MJ1267.(d) One of the two NCS-related molecules in the pyrophosphate-bound structure of MalK [17].Residues with side chains participating in alternative H bonding networks with phylogenetically conserved Arg166 are shown in cyan. Relative to MJ1267, homologous residues in the g-phosphate linker region are offset by +1 in MJ0796, +11 in HisP, and -1 in MalK, and homologous residues in the C terminus of the ABCa subdomain are offset by -8 in MJ0796, +0 in HisP, and -14 in MalK

The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 571-586) copyright 2001.

Figure was selected by an automated process.