ABC转运蛋白结构及其在细菌致病性中的研究进展

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

摘要/Abstract

摘要：

ABC转运蛋白,即腺苷三磷酸结合盒转运蛋白（ATP-binding cassette transporter）是具有多种功能且分布极为广泛的膜蛋白质家族。它的主要功能是利用ATP水解产生的能量来实现对底物的跨膜转运,ABC超家族蛋白转运体普遍存在于细菌、真菌,线虫,果蝇、植物、哺乳动物等几乎所有生物体内。大多数ABC 转运蛋白最初是通过研究真核生物体耐药性（多效耐药和多药耐药）而被发现的。目前针对ABC转运蛋白在细菌致病性中所发挥作用也有广泛的研究。本文综述了ABC 转运蛋白的结构、转运机制和ABC转运蛋白在细菌致病性过程中的作用,讨论了深入研究ABC转运蛋白作用机制对细菌性疾病防治的意义及存在问题。ABC转运蛋白相关的细胞表面或分泌因子很可能是抗菌疗法或疫苗开发的作用靶点,为细菌性疾病的预防提供了新的思路。

关键词: ABC转运蛋白, 原核生物, 致病性, 毒力, 耐药性

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

陈福暖, 黄瑜, 蔡佳, 王忠良, 简纪常, 王蓓. ABC转运蛋白结构及其在细菌致病性中的研究进展[J]. 生物技术通报, 2022, 38(6): 43-52.

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.

图/表 5

表1 核苷酸结合结构域保守基序的功能

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

图1 NBD二聚体结构示意图（Orelle）同源二聚体（左图）、异源二聚体（右图）;A：A环,WA：Walker-A,Q：Q环,WB：Walker-B,E：E环,H：H环,NBS：核苷酸结合位点,C：C环,D：D环

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

图2 ABC转运体结构（Locher） A：金黄色葡萄球菌多药转运蛋白Sav1866;B：闪烁古生球菌钼酸盐/钨酸转运体ModBC-A41;C：大肠杆菌维生素B12转运蛋白BtuCD-F53;D：短乳杆菌内向转运蛋白cfAST87

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

图3 ABC转运体功能示意图（Locher） A：ABC内向转运蛋白,利用底物结合蛋白（SBP）将亲水底物送入由TMDs形成的转运途径;B：ABC外向转运蛋白,TMD与NBD连通

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

图4 革兰氏阴性细胞中ABC转运蛋白参与细菌致病性的作用（Victoria） A：与毒素、细胞表面蛋白、铁载体、水解酶或抗菌肽分泌相关的I型分泌系统;B：糖缀合和多糖生物合成途径,涉及细胞膜合成和免疫逃逸;C：外排转运体;D：与诸如营养获取（如金属离子、氨基酸、维生素和寡肽）和渗透保护等过程有关

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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