生物技术通报 ›› 2022, Vol. 38 ›› Issue (6): 43-52.doi: 10.13560/j.cnki.biotech.bull.1985.2021-1175
收稿日期:
2021-09-14
出版日期:
2022-06-26
发布日期:
2022-07-11
作者简介:
陈福暖,男,硕士研究生,研究方向:水生动物医学;E-mail: 基金资助:
CHEN Fu-nuan(), HUANG Yu, CAI Jia, WANG Zhong-liang, JIAN Ji-chang, WANG Bei()
Received:
2021-09-14
Published:
2022-06-26
Online:
2022-07-11
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。
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.
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 |
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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