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 3b5x
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572 a.a.* *

* C-alpha coords only

* Residue conservation analysis
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PDB id: 3b5x
Name: Membrane protein
Title: Crystal structure of msba from vibrio cholerae

Structure:		 Lipid a export atp-binding/permease protein msba. Chain: a, b. Engineered: yes

Source: 		Vibrio cholerae. Organism_taxid: 666. Gene: msba. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

UniProt:
Chains A, B: Q9KQW9 (MSBA_VIBCH)
Pfam  
Seq:
Struc:
Seq:
Struc:
Seq: 582 a.a.
Struc: 572 a.a.
Key:    PfamA domain  Secondary structure

Resolution: 		5.50Å

R-factor: 		0.348

R-free: 		0.360

Authors: 		A.Ward,C.L.Reyes,J.Yu,C.B.Roth,G.Chang

Key ref:
A.Ward et al. (2007). Flexibility in the ABC transporter MsbA: Alternating access with a twist.. Proc Natl Acad Sci U S A, 104, 19005-19010. [PubMed id: 18024585] [DOI: 10.1073/pnas.0709388104]

Date: 		26-Oct-07

Release date: 		04-Dec-07

Related entries: 		3b5w
crystal structure of eschericia coli msba
3b5y
crystal structure of msba from salmonella typhimurium with
amppnp
3b5z
crystal structure of msba from salmonella typhimurium with
adp vanadate
3b60
crystal structure of msba from salmonella typhimurium with
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    Key reference    
 
 
DOI no: 10.1073/pnas.0709388104 Proc Natl Acad Sci U S A 104:19005-19010 (2007)
PubMed id: 18024585  
 
 
Flexibility in the ABC transporter MsbA: Alternating access with a twist.
A.Ward, C.L.Reyes, J.Yu, C.B.Roth, G.Chang.
 
  ABSTRACT  
 
ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a wide variety of substrates across cellular membranes and are conserved from bacteria to humans. Here we compare four x-ray structures of the bacterial ABC lipid flippase, MsbA, trapped in different conformations, two nucleotide-bound structures and two in the absence of nucleotide. Comparison of the nucleotide-free conformations of MsbA reveals a flexible hinge formed by extracellular loops 2 and 3. This hinge allows the nucleotide-binding domains to disassociate while the ATP-binding half sites remain facing each other. The binding of the nucleotide causes a packing rearrangement of the transmembrane helices and changes the accessibility of the transporter from cytoplasmic (inward) facing to extracellular (outward) facing. The inward and outward openings are mediated by two different sets of transmembrane helix interactions. Altogether, the conformational changes between these structures suggest that large ranges of motion may be required for substrate transport.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Stereoviews of three conformations of MsbA. (A) Nucleotide bound. (B) Open apo. (C) Closed apo. One monomer in each model is colored with a rainbow gradient (N terminus is blue, C terminus is red), and the other is white. TM helices (TM1–TM6), extracellular loops (EL1–EL3), and intracellular helices (IH1–IH2) are labeled accordingly. AMPPNP molecules are displayed as blue sticks in the nucleotide-bound structure. In all structures, TM4/TM5/IH2 (yellow and orange) associates with the opposite monomer in a conserved manner. 		Figure 5.
Fig. 5. Summary of conformational changes in MsbA. (A) Conformational changes within the MsbA dimer alter the accessibility to the internal chamber from inward to outward facing. For clarity, only TM helices (labeled 1–6) of one monomer (cyan) are shown inside a surface rendering of the dimer. The open and closed apo conformations form an inward-facing V between TM4/TM5 and TM3/TM6 (red asterisk). The nucleotide-bound conformation (MsbA-AMPPNP) forms an outward-facing V between TM3/TM6 and TM1/TM2, just above the elbow helix (black asterisk). Upon nucleotide binding, TM4/TM5/IH2 moves, causing TM3/TM6 to split away from TM1/TM2, which results in an outward-facing conformation. Both inward- and outward-facing conformations are mediated by intramolecular interactions within a single monomer, but by different sets of helices. (B) Simplified cartoon model illustrating the points above. The relative position of each TM helix is labeled with a number (one monomer in white and the other in gray). The arrows illustrate the motions required to go to the next state. (C) Top-down view of NBDs (one monomer shown in white and the other in gray). IH1 (green) and IH2 (yellow) from both monomers are shown. In the absence of nucleotide (apo), the NBDs are in similar orientations with the ATP-binding half-sites (LSGGQ and P-loop) facing each other; the P-loops (red) are roughly aligned (dashed lines) with one another across the dimer interface. Upon nucleotide binding (AMPPNP - magenta), the canonical ATP sandwich is formed, aligning the nucleotide between the LSGGQ and P-loop. IH1 tracks with the cis-monomer, whereas IH2 tracks with the trans-monomer. The motion of the NBDs from closed-apo- to nucleotide-bound transmits a structural change (described above) to the TMs via IH1 and IH2, resulting in an outward-facing conformation.
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference
  PubMed id Reference
19132955 A.Siarheyeva, and F.J.Sharom (2009).
The ABC transporter MsbA interacts with lipid A and amphipathic drugs at different sites.
  Biochem J, 419, 317-328.  
  19732422 A.W.Ravna, I.Sylte, and G.Sager (2009).
Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure.
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19238460 A.W.Ravna, I.Sylte, and S.G.Dahl (2009).
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19754156 C.Alexander, A.Ivetac, X.Liu, Y.Norimatsu, J.R.Serrano, A.Landstrom, M.Sansom, and D.C.Dawson (2009).
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  Biochemistry, 48, 10078-10088.  
19339978 D.C.Gadsby (2009).
Ion channels versus ion pumps: the principal difference, in principle.
  Nat Rev Mol Cell Biol, 10, 344-352.  
19234479 D.C.Rees, E.Johnson, and O.Lewinson (2009).
ABC transporters: the power to change.
  Nat Rev Mol Cell Biol, 10, 218-227.  
19053133 D.Parcej, and R.Tampé (2009).
Solute-binding sites in ABC transporters for recognition, occlusion and trans-inhibition.
  ChemMedChem, 4, 25-28.  
19418088 G.K.Wang, J.Calderon, S.J.Jaw, and S.Y.Wang (2009).
State-dependent block of Na+ channels by articaine via the local anesthetic receptor.
  J Membr Biol, 229, 1-9.  
19297616 G.Oancea, M.L.O'Mara, W.F.Bennett, D.P.Tieleman, R.Abele, and R.Tampé (2009).
Structural arrangement of the transmission interface in the antigen ABC transport complex TAP.
  Proc Natl Acad Sci U S A, 106, 5551-5556.  
18955484 H.T.Lin, V.N.Bavro, N.P.Barrera, H.M.Frankish, S.Velamakanni, H.W.van Veen, C.V.Robinson, M.I.Borges-Walmsley, and A.R.Walmsley (2009).
MacB ABC Transporter Is a Dimer Whose ATPase Activity and Macrolide-binding Capacity Are Regulated by the Membrane Fusion Protein MacA.
  J Biol Chem, 284, 1145-1154.  
19159494 J.P.Becker, G.Depret, F.Van Bambeke, P.M.Tulkens, and M.Prévost (2009).
Molecular models of human P-glycoprotein in two different catalytic states.
  BMC Struct Biol, 9, 3.  
19707853 J.P.Mornon, P.Lehn, and I.Callebaut (2009).
Molecular models of the open and closed states of the whole human CFTR protein.
  Cell Mol Life Sci, 66, 3469-3486.  
19479721 M.A.Do Cao, S.Crouzy, M.Kim, M.Becchi, D.S.Cafiso, A.Di Pietro, and J.M.Jault (2009).
Probing the conformation of the resting state of a bacterial multidrug ABC transporter, BmrA, by a site-directed spin labeling approach.
  Protein Sci, 18, 1507-1520.  
19633680 N.Ruiz, D.Kahne, and T.J.Silhavy (2009).
Transport of lipopolysaccharide across the cell envelope: the long road of discovery.
  Nat Rev Microbiol, 7, 677-683.  
19171975 P.D.Jeffrey (2009).
Analysis of errors in the structure determination of MsbA.
  Acta Crystallogr D Biol Crystallogr, 65, 193-199.  
19325113 S.G.Aller, J.Yu, A.Ward, Y.Weng, S.Chittaboina, R.Zhuo, P.M.Harrell, Y.T.Trinh, Q.Zhang, I.L.Urbatsch, and G.Chang (2009).
Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding.
  Science, 323, 1718-1722.
PDB codes: 3g5u 3g60 3g61
19593434 S.Velamakanni, C.H.Lau, D.A.Gutmann, H.Venter, N.P.Barrera, M.A.Seeger, B.Woebking, D.Matak-Vinkovic, L.Balakrishnan, Y.Yao, E.C.U, R.A.Shilling, C.V.Robinson, P.Thorn, and H.W.van Veen (2009).
A multidrug ABC transporter with a taste for salt.
  PLoS One, 4, e6137.  
19544044 V.Kos, and R.C.Ford (2009).
The ATP-binding cassette family: a structural perspective.
  Cell Mol Life Sci, 66, 3111-3126.  
18535149 A.L.Davidson, E.Dassa, C.Orelle, and J.Chen (2008).
Structure, function, and evolution of bacterial ATP-binding cassette systems.
  Microbiol Mol Biol Rev, 72, 317.  
18305154 A.W.Serohijos, T.Hegedus, A.A.Aleksandrov, L.He, L.Cui, N.V.Dokholyan, and J.R.Riordan (2008).
Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function.
  Proc Natl Acad Sci U S A, 105, 3256-3261.  
18768814 B.Ma, C.M.Reynolds, and C.R.Raetz (2008).
Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant.
  Proc Natl Acad Sci U S A, 105, 13823-13828.  
18658148 L.He, A.A.Aleksandrov, A.W.Serohijos, T.Hegedus, L.A.Aleksandrov, L.Cui, N.V.Dokholyan, and J.R.Riordan (2008).
Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate regulation of channel gating.
  J Biol Chem, 283, 26383-26390.  
18721111 M.A.Demel, R.Schwaha, O.Krämer, P.Ettmayer, E.E.Haaksma, and G.F.Ecker (2008).
In silico prediction of substrate properties for ABC-multidrug transporters.
  Expert Opin Drug Metab Toxicol, 4, 1167-1180.  
18644782 S.Pagant, E.Y.Brovman, J.J.Halliday, and E.A.Miller (2008).
Mapping of interdomain interfaces required for the functional architecture of Yor1p, a eukaryotic ATP-binding cassette (ABC) transporter.
  J Biol Chem, 283, 26444-26451.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.