Structure of ABC Transporter and Research Progress of It in Bacterial Pathogenicity

doi:10.13560/j.cnki.biotech.bull.1985.2021-1175

Abstract

Abstract:

Adenosine triphosphate binding cassette transporter（ATP-binding cassette transporter,ABC transporter）is known as the most numerous protein family with multiple roles. Functionally,ABC transporter mediate the cross-membrance transmission of multiple substrates by using the energy generated by ATP hydrolysis. ABC transporters exist in most organisms including bacteria,fungi,nematodes,fruit flies,plants,and mammals. Most of ABC transporters were originally discovered by studying the drug resistance（multiple drug resistance and multidrug resistance）of eukaryotes. Recently,there are broad researches on the roles of ABC transporters in bacterial pathogenicity. This paper summarized the structure and mechanism of ABC transporter and the role of it in bacterial pathogenicity,discussed the significance and issues in further studying the mechanism of ABC transporter and control of bacterial diseases. The cell surface or secretory factors associated with ABC transporters is potential targets of antimicrobial therapy or vaccine development,which provides a new idea for the prevention of bacterial diseases.

Key words: ATP-binding cassette, prokaryotes, pathogenicity, virulence, drug resistance

CHEN Fu-nuan, HUANG Yu, CAI Jia, WANG Zhong-liang, JIAN Ji-chang, WANG Bei. Structure of ABC Transporter and Research Progress of It in Bacterial Pathogenicity[J]. Biotechnology Bulletin, 2022, 38(6): 43-52.

Figures/Tables 5

Table 1 Functions of conserved motifs in the nucleotide-binding domain

基序Motif	共有序列Consensus sequence	功能Function	代表性蛋白Repretative proteins
Walker A	Gxx Gx GKST	ATP binding	His P,MJ0796,MJ1267,Rad50,TAP1,GlcV,E.c.Mal K
Q loop	Q0	a. TM subunit interaction b. Q H-bond to Mg c. Binding to the attacking water	a. Btu CD b.MJ0796（E171Q）,Glc V/ADP c.MJ0796（E171Q）
Signature motif	LSGGQx QR	ATP binding	Rad50,MJ0796（E171Q）,E.c.Mal K
Walker B	hhhh D	D makes a water-bridged contact with Mg²⁺	Glc V（Mg ADP,Mg AMPPNP）,MJ1267（Mg ADP）,MJ0796（Mg ADP）
D loop	E following Walker B	a. Binds to attacking water b.Binds to Mg through a water	a. MJ0796（E171Q） b. Glc V（Mg ADP,Mg AMPPNP）
H motif or Switch region	H	His H-bond to-phosphate	MJ0796（E171Q）,E.c.Mal K

Fig. 1 Schematic diagram of NBD dimer structure（Orelle） Homodimers（left panel）,heterodimers（right panel）;A：A-loop. WA：Walker-A. Q：Q-loop. WB：Walker-B. E：E-loop. H：H-loop. NBS：Nucleotide binding site. C：C-loop. D：D-loop

Fig. 2 Structure of ABC transporter（Locher） A：Staphylococcus aureus multidrug transporter Sav1866. B：Archaeoglobus fulgidus molybdate/tungstate transporter ModBC-A41. C：E. coli vitamin B12 transporter BtuCD-F53. D：Lactobacillus brevis folate importer EcfAST87

Fig. 3 Schematic diagram of ABC transporter function（Locher） A：ABC importers,which require a substrate binding protein（SBP）that feeds the hydrophilic substrates into the translocation pathway formed by the TMDs. B：ABC exporters,which typically have their TMDs fused to the ABCs

Fig. 4 Roles associated with ABC transporters involved in bacterial pathogenicity in a model Gram-negative cell（Victoria） A：Type I secretions systems associated with toxin,S-layer protein,siderophore,hydrolytic enzyme or antimicrobial peptide secretion;B：glycoconjugate and polysaccharide biogenesis pathways,which are involved in membrane biogenesis and immune evasion;C：Efflux transporters;D：Associated with processes such as nutrient acquisition（e.g. metal ions,amino acids,vitamins and oligopeptides）and osmoprotection

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