title: Dimer opening of the nucleotide binding domains of ABC transporters after ATP hydrolysis.
abstract: 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.
authors.affiliation: Department of Biochemistry, Center for Biophysics and Computational Biology, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Po-Chao
authors.initials: PC
authors.lastname: Wen
authors.forename: Emad
authors.initials: E
authors.lastname: Tajkhorshid
mesh_terms: 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
chemical_list: D018528:ATP-Binding Cassette Transporters; D029968:Escherichia coli Proteins; C489398:MalK protein, E coli; D005973:Glutamine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate
references.citation: Biochemistry. 2007 Mar 13;46(10):2767-78
references.pmid: 17302441
references.citation: J Biol Chem. 2003 Jul 18;278(29):26862-9
references.pmid: 12746444
references.citation: J Biol Chem. 2007 Aug 3;282(31):22793-803
references.pmid: 17485460
references.citation: Science. 2008 Jul 11;321(5886):250-3
references.pmid: 18621668
references.citation: J Bioenerg Biomembr. 2004 Feb;36(1):5-15
references.pmid: 15168605
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5069-74
references.pmid: 18356296
references.citation: Proteins. 2004 Nov 15;57(3):635-8
references.pmid: 15382245
references.citation: J Mol Biol. 2003 Jul 4;330(2):343-58
references.pmid: 12823973
references.citation: J Biol Chem. 2002 May 3;277(18):15419-25
references.pmid: 11861646
references.citation: J Mol Biol. 2003 Nov 21;334(2):255-67
references.pmid: 14607117
references.citation: FEBS Lett. 2005 Aug 1;579(19):4193-9
references.pmid: 16038903
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2006 Mar;372(6):385-99
references.pmid: 16541253
references.citation: J Biol Chem. 2005 Jan 14;280(2):1346-53
references.pmid: 15528182
references.citation: J Biol Chem. 2004 Nov 5;279(45):46518-26
references.pmid: 15326176
references.citation: Annu Rev Biochem. 2004;73:241-68
references.pmid: 15189142
references.citation: FEBS Lett. 2007 Mar 6;581(5):935-8
references.pmid: 17303126
references.citation: EMBO J. 2004 Jan 28;23(2):282-93
references.pmid: 14685259
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Biol Chem. 2004 Oct;385(10):927-33
references.pmid: 15551867
references.citation: J Comput Chem. 2004 Aug;25(11):1400-15
references.pmid: 15185334
references.citation: Mol Microbiol. 2006 May;60(3):542-52
references.pmid: 16629659
references.citation: Nature. 1998 Dec 17;396(6712):703-7
references.pmid: 9872322
references.citation: Science. 2007 Jan 19;315(5810):373-7
references.pmid: 17158291
references.citation: Mol Cell. 2002 Jul;10(1):139-49
references.pmid: 12150914
references.citation: Mol Cell. 2003 Sep;12(3):651-61
references.pmid: 14527411
references.citation: J Comput Chem. 2005 Dec;26(16):1781-802
references.pmid: 16222654
references.citation: Biochemistry. 2005 Jul 19;44(28):9680-90
references.pmid: 16008353
references.citation: J Bacteriol. 1997 Sep;179(17):5458-64
references.pmid: 9287001
references.citation: J Biol Chem. 1997 Aug 29;272(35):21883-91
references.pmid: 9268321
references.citation: Annu Rev Genomics Hum Genet. 2005;6:123-42
references.pmid: 16124856
references.citation: J Biol Chem. 2003 Aug 8;278(32):29546-51
references.pmid: 12766159
references.citation: J Biol Chem. 2004 Oct 22;279(43):45013-9
references.pmid: 15308647
references.citation: J Biol Chem. 2006 Sep 22;281(38):28397-407
references.pmid: 16877382
references.citation: J Gen Physiol. 2003 Sep;122(3):333-48
references.pmid: 12939393
references.citation: EMBO J. 2006 Jul 26;25(14):3432-43
references.pmid: 16858415
references.citation: Curr Opin Struct Biol. 2007 Aug;17(4):412-8
references.pmid: 17723295
references.citation: Science. 2008 Jul 11;321(5886):246-50
references.pmid: 18511655
references.citation: Nature. 2007 Mar 8;446(7132):213-6
references.pmid: 17322901
references.citation: EMBO J. 2005 Jun 1;24(11):1901-10
references.pmid: 15889153
references.citation: J Biol Chem. 1999 Sep 17;274(38):26727-35
references.pmid: 10480876
references.citation: J Biol Chem. 1990 Mar 15;265(8):4254-60
references.pmid: 2155217
references.citation: Nat Struct Mol Biol. 2004 Oct;11(10):918-26
references.pmid: 15452563
references.citation: Microbiol Mol Biol Rev. 2007 Sep;71(3):463-76
references.pmid: 17804667
references.citation: Mol Membr Biol. 2005 Jan-Apr;22(1-2):29-39
references.pmid: 16092522
references.citation: Biochim Biophys Acta. 2007 Jun;1775(2):237-62
references.pmid: 17572300
references.citation: Biochem J. 2005 Mar 15;386(Pt 3):489-95
references.pmid: 15636583
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19005-10
references.pmid: 18024585
references.citation: J Biol Chem. 2002 Jun 14;277(24):21111-4
references.pmid: 11964392
references.citation: Nature. 2007 Nov 22;450(7169):515-21
references.pmid: 18033289
references.citation: Mol Microbiol. 2007 Jul;65(2):250-7
references.pmid: 17578454
references.citation: Science. 2007 Sep 7;317(5843):1387-90
references.pmid: 17673622
references.citation: Science. 2002 May 10;296(5570):1091-8
references.pmid: 12004122
references.citation: Nature. 2006 Mar 23;440(7083):477-83
references.pmid: 16554808
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17969-74
references.pmid: 16326809
references.citation: Biophys J. 2007 Apr 15;92(8):2727-34
references.pmid: 17208973