Characterization of a Novel Domain 'GATE' in the ABC Protein DrrA and Its Role in Drug Efflux by the DrrAB Complex

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2015 Feb 28

PMID 25721665

Citations 5

Authors

Han Zhang

Sadia Rahman

Wen Li

Guoxing Fu

Parjit Kaur

Affiliations

Soon will be listed here.

Abstract

A novel domain, GATE (Glycine-loop And Transducer Element), is identified in the ABC protein DrrA. This domain shows sequence and structural conservation among close homologs of DrrA as well as distantly-related ABC proteins. Among the highly conserved residues in this domain are three glycines, G215, G221 and G231, of which G215 was found to be critical for stable expression of the DrrAB complex. Other conserved residues, including E201, G221, K227 and G231, were found to be critical for the catalytic and transport functions of the DrrAB transporter. Structural analysis of both the previously published crystal structure of the DrrA homolog MalK and the modeled structure of DrrA showed that G215 makes close contacts with residues in and around the Walker A motif, suggesting that these interactions may be critical for maintaining the integrity of the ATP binding pocket as well as the complex. It is also shown that G215A or K227R mutation diminishes some of the atomic interactions essential for ATP catalysis and overall transport function. Therefore, based on both the biochemical and structural analyses, it is proposed that the GATE domain, located outside of the previously identified ATP binding and hydrolysis motifs, is an additional element involved in ATP catalysis.

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References

Gerber S, Comellas-Bigler M, Goetz B, Locher K . Structural basis of trans-inhibition in a molybdate/tungstate ABC transporter. Science. 2008; 321(5886):246-50. DOI: 10.1126/science.1156213. View

Kadaba N, Kaiser J, Johnson E, Lee A, Rees D . The high-affinity E. coli methionine ABC transporter: structure and allosteric regulation. Science. 2008; 321(5886):250-3. PMC: 2527972. DOI: 10.1126/science.1157987. View

Fu G, Chumanevich A, Agniswamy J, Fang B, Harrison R, Weber I . Structural basis for executioner caspase recognition of P5 position in substrates. Apoptosis. 2008; 13(11):1291-302. PMC: 2782447. DOI: 10.1007/s10495-008-0259-9. View

Pradhan P, Li W, Kaur P . Translational coupling controls expression and function of the DrrAB drug efflux pump. J Mol Biol. 2008; 385(3):831-42. DOI: 10.1016/j.jmb.2008.11.027. View

Aller S, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R . Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009; 323(5922):1718-22. PMC: 2720052. DOI: 10.1126/science.1168750. View

Fang B, Fu G, Agniswamy J, Harrison R, Weber I . Caspase-3 binds diverse P4 residues in peptides as revealed by crystallography and structural modeling. Apoptosis. 2009; 14(5):741-52. DOI: 10.1007/s10495-009-0333-y. View

Emsley P, Lohkamp B, Scott W, Cowtan K . Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. PMC: 2852313. DOI: 10.1107/S0907444910007493. View

Zhang H, Pradhan P, Kaur P . The extreme C terminus of the ABC protein DrrA contains unique motifs involved in function and assembly of the DrrAB complex. J Biol Chem. 2010; 285(49):38324-36. PMC: 2992266. DOI: 10.1074/jbc.M110.131540. View

Smith P, Karpowich N, Millen L, Moody J, Rosen J, Thomas P . ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol Cell. 2002; 10(1):139-49. PMC: 3516284. DOI: 10.1016/s1097-2765(02)00576-2. View

10.

Saveanu L, Daniel S, van Endert P . Distinct functions of the ATP binding cassettes of transporters associated with antigen processing: a mutational analysis of Walker A and B sequences. J Biol Chem. 2001; 276(25):22107-13. DOI: 10.1074/jbc.M011221200. View

11.

Li W, Sharma M, Kaur P . The DrrAB efflux system of Streptomyces peucetius is a multidrug transporter of broad substrate specificity. J Biol Chem. 2014; 289(18):12633-46. PMC: 4007453. DOI: 10.1074/jbc.M113.536136. View

12.

Chen J, Lu G, Lin J, Davidson A, Quiocho F . A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. Mol Cell. 2003; 12(3):651-61. DOI: 10.1016/j.molcel.2003.08.004. View

13.

Borges-Walmsley M, McKeegan K, Walmsley A . Structure and function of efflux pumps that confer resistance to drugs. Biochem J. 2003; 376(Pt 2):313-38. PMC: 1223791. DOI: 10.1042/BJ20020957. View

14.

Solomon K, Hsu D, Brusilow W . Use of lacZ fusions to measure in vivo expression of the first three genes of the Escherichia coli unc operon. J Bacteriol. 1989; 171(6):3039-45. PMC: 210012. DOI: 10.1128/jb.171.6.3039-3045.1989. View

15.

Guilfoile P, Hutchinson C . A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. Proc Natl Acad Sci U S A. 1991; 88(19):8553-7. PMC: 52547. DOI: 10.1073/pnas.88.19.8553. View

16.

Kaur P . Expression and characterization of DrrA and DrrB proteins of Streptomyces peucetius in Escherichia coli: DrrA is an ATP binding protein. J Bacteriol. 1997; 179(3):569-75. PMC: 178733. DOI: 10.1128/jb.179.3.569-575.1997. View

17.

Guex N, Peitsch M . SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1998; 18(15):2714-23. DOI: 10.1002/elps.1150181505. View

18.

Kaur P, Russell J . Biochemical coupling between the DrrA and DrrB proteins of the doxorubicin efflux pump of Streptomyces peucetius. J Biol Chem. 1998; 273(28):17933-9. DOI: 10.1074/jbc.273.28.17933. View

19.

Coleman M, Bass R, Mehan R, Falke J . Conserved glycine residues in the cytoplasmic domain of the aspartate receptor play essential roles in kinase coupling and on-off switching. Biochemistry. 2005; 44(21):7687-95. PMC: 2895725. DOI: 10.1021/bi0501479. View

20.

Zaitseva J, Jenewein S, Jumpertz T, Holland I, Schmitt L . H662 is the linchpin of ATP hydrolysis in the nucleotide-binding domain of the ABC transporter HlyB. EMBO J. 2005; 24(11):1901-10. PMC: 1142601. DOI: 10.1038/sj.emboj.7600657. View