Diskussion:ABC-Transporter

Chloroquin Resistenz

"ABC-Transporter vermitteln dem Malaria-Erreger Plasmodium die Resistenz gegen Malariamedikamente"

Das ist so nicht richtig, auch wenn es in den meisten Lehrbüchern so zu lesen ist.

Die Chloroquinresistenz wird wahrscheinlich von einem Protein namens PfCRT vermittelt. Das momentane Modell geht davon aus, dass es sich um einen Carrier, genauer gesagt einen Symporter handelt. Er geht durch eine Punktmutation von einem "exchange-only-carrier" hervor. (Der vorstehende nicht signierte Beitrag – siehe dazu Hilfe:Signatur – stammt von 78.51.64.179 (Diskussion • Beiträge) 19:44, 15. Okt. 2007 (CET))

Das ist so nicht richtig. Zitat UniProt P13568: P.falciparum resistant to the drug chloroquine have multiple copies of the gene coding for MDR. Aus dem Eintrag ist ersichtlich, dass es sich um einen ABC-Transporter handelt. --Ayacop 15:59, 2. Nov. 2008 (CET)

Dimerbildung

Eine der wichtigsten Unterschiede zwischen den ABC-Transportern in Eu- und Prokaryoten ist, dass in Prokaryoten (alle Im- und Exporter) ein ABC-Transporter aus zwei Polypeptiden besteht. Das bedeutet, der funtkionelle Transporter muss ein Dimer sein (Homo- oder Heterodimer). In Eukaryoten bestehen ABC-Transporter (immer Exporter) hingegen aus nur einem Polypeptid. Es handelt sich also immer um ein Monomer! (nicht signierter Beitrag von 85.182.32.51 (Diskussion) 11:38, 1. Mär. 2011 (CET))

FALSCH!!!

"The ABC transporters are one of the largest families of active transport molecules. These transporter are abundant in the genomes of all organisms, and are nearly always import pumps in prokaryotes and involved in efflux in eukaryotic cells. The well characterized eukaryotic transporters all transport sunstances from the cytoplasm or plasma membrane out of cell, or into organelles such as the peroxisome, endoplasmic reticulum, and lysosomes. In addition, four transporters are localized to the mitochondria." [Robert W. Robey et. al., "ABCG2: A perspective", Adv Drug Deliv Rev. 2009 Jan 31;61(1):3-13. Epub 2008 Dec 16]

"Based on their predicted two-dimensional structure in membranes, the drug efflux transporters discussed here can be divided into four classes (Fig. 1). Discovered first, the P-glycoprotein polypeptide consists of two very similar halves, each containing 6 putative transmembrane segments, and an intracellular ATP binding site. The first extracellular loop in P-gp is heavily N-glycosylated. The same overall architecture is found in MRP4 and MRP5, two members of the MRP family, but N-linked glycosylation occurs most likely on the fourth extracellular loop here. MRP1, MRP2, and MRP3 have the same basic structure as MRP4 and MRP5, but in addition they have an N-terminal extension consisting of 5 putative transmembrane segments. As a consequence, the N-terminus of these proteins is located extracellularly, and also glycosylated in MRP1. The most recently discovered ABC drug efflux transporter is BCRP. Unlike the discussed transporters, this is a half-transporter, consisting of only a single N-terminal, intracellular ATP binding site, followed by 6 putative transmembrane segments. The last extracellular loop is in all likelihood N-glycosylated [10]. Based on analogy with the other mammalian ABC drug transporters and bacterial ABC drug ‘half’-transporters such as LmrA and MsbA [11] and [12], and biochemical data [13], [14] and [15] it is very likely that BCRP functions as a homodimer. All the transporters possess to a greater or lesser extent extracellular N-glycosylation branches (Fig. 1). Based on in vitro studies on P-gp [16] it appears that this N-glycosylation is not necessary for the basic transport function of these transporters. However, N-glycosylation probably has an important cell-biological role for these proteins, helping in stabilizing membrane insertion and possibly routing to, and stability in the plasma membrane." [Schinkel AH, Jonker JW., "Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview", Adv Drug Deliv Rev. 2003 Jan 21;55(1):3-29.]

Structure of ABCG2

"All human ABC transporters have a distinctive modular architecture, consisting of at least one hydrophilic nucleotide binding domain (NBD) located in cytoplasm and one hydrophobic membrane-spanning domain (MSD). Based on the structure and arrangement of NBD and MSD, they can be grouped into ‘full transporters’, ‘half transporters’ and non-transporter type ABC proteins [8]. Typically, full transporters, such as ABCB1, comprise two homologous halves and are characterized by two MSDs and two NBDs with an arrangement of MSD1-NBD1- MSD2-NBD2. Other types of full transporters, such as ABCC1, have an extra MSD (MSD0) at the amino terminus with a domain structure of MSD0-MSD1-NBD1-MSD2-NBD2. Half transporters contain only one MSD and one NBD, which are about half the size of a full transporter. These half transporters include members of the ABCD subfamily and some of the ABCB subfamily with a domain structure of MSD-NBD, and members of the ABCG subfamily with a reversed NBD-MSD configuration. The non-transporter ABC proteins include members of the ABCE and ABCF subfamilies that do not have MSDs.

Human ABCG2 is a half transporter with a domain structure of NBD-MSD and the MSD consists of 6 putative transmembrane (TM) segments (Figure 1). This topological folding of ABCG2 with 6 TM segments has been demonstrated using epitope tagging although the exact location of the TM segments is slightly different from the original prediction [9]. The previously predicted TM2 and TM5 are shifted to the extracellular and intracellular loops in the new model, respectively. Further studies are needed to verify the exact location of these two TM segments and the new sequences that now function as TM2 and TM5. Nevertheless, future studies of the MSD of ABCG2 need to take into consideration of the possible alteration in the TM segment assignments."

"However, emerging evidence suggest that ABCG2 may exist as a higher order of homo-oligomer on plasma membranes." [Mo W, Zhang JT.,"Human ABCG2: structure, function, and its role in multidrug resistance.", Int J Biochem Mol Biol. 2012;3(1):1-27. Epub 2011 Mar 30.]Loki.mm21 (Diskussion) 11:39, 20. Aug. 2012 (CEST)

Neuauflage dringend notwendig!

Also nachdem ich mir diesen Artikel hier bei Wikipedia mehrmals durchgelesen habe, kann ich ihm nur die Note 4 geben. Er ist in vielen Bereichen ungenau und fehlerhaft! Werde ihn daher im Laufe der Zeit vollig neu schreiben. Wird aber ein Weilchen dauern. Da ich gerade im Begriff bin mich in diese Materie genauer einzulesen. Beschäftige mich seit einer Woche beruflich mit dem BCRP/ABCG2 einem bedeutenden Vertreter der ABC-Familie.Loki.mm21 (Diskussion) 11:42, 20. Aug. 2012 (CEST)