ABC transporter

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ABC transporter
ABC transporter
Ribbon representation of the vitamin B 12 transporter-like ABC transporter (BtuCD) according to PDB  1l7v
Transporter classification
TCDB 3.A.1
designation ABC Transporter Superfamily
Enzyme classification
EC, category 3.6.3.- ,  hydrolase
Substrate Substrate (in / out) + ATP
Products Substrate (out / in) + adenosine diphosphate + phosphate

ABC transporters are a large family of membrane proteins , which as a common structural element is an ATP -binding cassette (of English: ATP binding cassette, ABC ) possess specific substrates running over a cell membrane transport.

General

If the substrates are transported by ABC transporters against a concentration gradient, energy has to be expended for the process; this happens through the binding and hydrolysis of ATP to the ABC unit. ABC transporters belong to the primarily active transporters on the one hand and to the membrane-bound ATPases on the other hand.

The ABC transporter superfamily comprises one of the largest protein families known, with members in almost every organism, from bacteria to mammals . Plants also have ABC transporters. The ABC transporters are expressed in most of the secreting epithelia, including the liver and intestines , in humans . The ABC vans have attracted attention in recent years when it has been recognized that they have significant medical, industrial, and economic importance. They play a major role in the resistance of potentially pathogenic bacteria to antibiotics and antimycotics and in the case of plants in the resistance to herbicides . In humans, mutations in a gene that codes for an ABC transporter can lead to various metabolic diseases. Strong expression of the ABC transporter in tumor tissues often causes chemotherapy to fail.

All eukaryotic ABC transporters are exporters. Some are very substrate specific, others multispecific. All ABC transporters are active transporters, as the ATP binding and hydrolysis drive the transport process. A well-known exception is CFTR ( Cystic Fibrosis Transmembrane Conductance Regulator ), as the ABC cassette only controls the opening and closing of the chloride ion channel. The CFTR is therefore a chloride ion channel with a sulphonyl receptor (SUR1) that acts as a regulator of the ion channel. The mutation of both alleles of the CFTR gene leads to so-called cystic fibrosis (cystic fibrosis) . This creates a tough mucus in the lungs and digestive tract, which leads to a tendency towards infectious diseases.

A eukaryotic ABC transporter is usually present as a dimer , with each of the monomers consisting of a hydrophobic transmembrane domain (TMD) and a hydrophilic domain containing the ATP-binding cassette. The hydrophobic permease domain mediates the transport of the substrate and is responsible for the specificity. In humans, most of the 49 known ABC transporters are monomers, but they also consist of a total of two TMD and two ATP-binding cassettes. Prokaryotic ABC transporters are usually tetramers made up of two membrane-spanning permease subunits, which do the actual transport, and two ATPase subunits. According to the current state of knowledge, the ATPase subunits specifically bind “their” permease subunit. A functional transporter can consist of two different PermeaseUEs and ATPaseUEs, as well as two homodimers, or a combination of homo- and heterodimers.

Subfamilies and members

The family of human ABC transporters can be divided into seven subfamilies (ABCA-G) with a total of 49 different genes and 21 different pseudogenes.

Subfamily name Member (genname) Coding chromosome
ABCA ABCA1 9
ABCA2 9
ABCA3 16
ABCA4 1
ABCA5 17th
ABCA6 17th
ABCA7 19th
ABCA8 17th
ABCA9 17th
ABCA10 17th
ABCA12 2
ABCA13 7th
ABCB ABCB1 7th
ABCB2 6th
ABCB3 6th
ABCB4 7th
ABCB5 7th
ABCB6 2
ABCB7 X
ABCB8 7th
ABCB9 12
ABCB10 1
ABCB11 2
ABCC ABCC1 16
ABCC2 10
ABCC3 17th
ABCC4 13
ABCC5 3
ABCC6 16
ABCC7 7th
ABCC8 (= SUR1 subunit of the ATP-sensitive potassium channel ) 11
ABCC9 12
ABCC10 6th
ABCC11 16
ABCC12 16
ABCC13 21st
ABCD ABCD1 X
ABCD2 12
ABCD3 1
ABCD4 14th
ABCE ABCE1 4th
ABCF ABCF1 6th
ABCF2 7th
ABCF3 3
ABCG ABCG1 21st
ABCG2 4th
ABCG4 11
ABCG5 2
ABCG8 2

Hereditary diseases

Defects in the function of the ABC transporter can trigger a wide variety of diseases . These include cystic fibrosis (cystic fibrosis) , Tangier's disease , adrenoleukodystrophy and special forms of spinocerebellar ataxia .

A defect in ABCC11 , on the other hand, is extremely common worldwide. For example, almost 100% of the Korean population. The defect does not lead to any disease, but rather causes, among other things, that the wearers of this feature have only a very weak body odor and white, dry ear wax .

Multiple drug resistance

The MDR1 transporter is the first ABC transporter to be characterized in humans. MDR stands for Multiple Drug Resistance and means something like "resistance to several drugs". Multiple Drug Resistance Protein 1 ( MDR 1 ) and Multidrug Resistance-Related Protein 1 (MRP1) are involved in the transporter.

MDR vans are coming a. in the blood-brain barrier , but also in tumor cells .

In the blood-brain barrier, for example, this type of transporter prevents the central effect of loperamide , an opioid .

The transporter can have an undesirable effect in cancer cells. Cancer cells with high MDR expression can show increased tolerance to cytostatics in the context of chemotherapy .

literature

Individual evidence

  1. ↑ Vasilis Vasiliou, Konstandinos Vasiliou and Daniel W. Nebert: Human ATP-binding cassette (ABC) transporter family . In: Human Genomics . 3, No. 3, 2009, pp. 281-290. doi : 10.1186 / 1479-7364-3-3-281 . PMC 2752038 (free full text).
  2. ↑ T. Ishikawa, Y. Toyoda, et al. a .: Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion. In: Frontiers in genetics. Volume 3, 2012, ISSN  1664-8021 , p. 306, doi : 10.3389 / fgene.2012.00306 , PMID 23316210 , PMC 3539816 (free full text). ( Open access )

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