Dimer opening of the nucleotide binding domains of ABC transporters after ATP hydrolysis.
ABC transporters constitute one of the most abundant membrane transporter families. The most common feature shared in the family is the highly conserved nucleotide binding domains (NBDs) that drive the transport process through binding and hydrolysis of ATP. Molecular dynamics simulations are used to investigate the effect of ATP hydrolysis in the NBDs. Starting with the ATP-bound, closed dimer of MalK, four simulation systems with all possible combinations of ATP or ADP-P(i) bound to the two nucleotide binding sites are constructed and simulated with equilibrium molecular dynamics for approximately 70 ns each. The results suggest that the closed form of the NBD dimer can only be maintained with two bound ATP molecules; in other words, hydrolysis of one ATP can lead to the opening of the dimer interface of the NBD dimer. Furthermore, we observed that the opening is an immediate effect of hydrolysis of ATP into ADP and P(i) rather than the dissociation of hydrolysis products. In addition, the opening is mechanistically triggered by the dissociation of the LSGGQ motif from the bound nucleotide. A metastable ADP-P(i) bound conformational state is consistently observed before the dimer opening in all the simulation systems.
Wen
Po-Chao
PC
Department of Biochemistry, Center for Biophysics and Computational Biology, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Tajkhorshid
Emad
E
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001665:Binding Sites; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D005973:Glutamine; D006868:Hydrolysis; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary
D018528:ATP-Binding Cassette Transporters; D029968:Escherichia coli Proteins; C489398:MalK protein, E coli; D005973:Glutamine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate
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