ABCB3 p.Ala374Asp
| Predicted by SNAP2: | C: D (59%), D: D (80%), E: D (80%), F: D (85%), G: N (61%), H: D (75%), I: D (75%), K: D (85%), L: D (85%), M: D (71%), N: D (75%), P: D (85%), Q: D (80%), R: D (80%), S: N (66%), T: D (63%), V: D (75%), W: D (80%), Y: D (85%), |
| Predicted by PROVEAN: | C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: D, V: D, W: D, Y: D, |
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[hide] The human transporter associated with antigen proc... J Biol Chem. 2012 Aug 10;287(33):28099-111. Epub 2012 Jun 14. Corradi V, Singh G, Tieleman DP
The human transporter associated with antigen processing: molecular models to describe peptide binding competent states.
J Biol Chem. 2012 Aug 10;287(33):28099-111. Epub 2012 Jun 14., [PMID:22700967]
Abstract [show]
The human transporter associated with antigen processing (TAP) is a member of the ATP binding cassette (ABC) transporter superfamily. TAP plays an essential role in the antigen presentation pathway by translocating cytosolic peptides derived from proteasomal degradation into the endoplasmic reticulum lumen. Here, the peptides are loaded into major histocompatibility class I molecules to be in turn exposed at the cell surface for recognition by T-cells. TAP is a heterodimer formed by the association of two half-transporters, TAP1 and TAP2, with a typical ABC transporter core that consists of two nucleotide binding domains and two transmembrane domains. Despite the availability of biological data, a full understanding of the mechanism of action of TAP is limited by the absence of experimental structures of the full-length transporter. Here, we present homology models of TAP built on the crystal structures of P-glycoprotein, ABCB10, and Sav1866. The models represent the transporter in inward- and outward-facing conformations that could represent initial and final states of the transport cycle, respectively. We described conserved regions in the endoplasmic reticulum-facing loops with a role in the opening and closing of the cavity. We also identified conserved pi-stacking interactions in the cytosolic part of the transmembrane domains that could explain the experimental data available for TAP1-Phe-265. Electrostatic potential calculations gave structural insights into the role of residues involved in peptide binding, such as TAP1-Val-288, TAP2-Cys-213, TAP2-Met-218. Moreover, these calculations identified additional residues potentially involved in peptide binding, in turn verified with replica exchange simulations performed on a peptide bound to the inward-facing models.
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No. Sentence Comment
190 The mutation A374D in human TAP2 influences the efficiency of binding as well as the peptide transport specificity (67).
X
ABCB3 p.Ala374Asp 22700967:190:13
status: NEW211 It has been shown that A374D alters the peptide transport specificity (67).
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ABCB3 p.Ala374Asp 22700967:211:23
status: NEW188 The mutation A374D in human TAP2 influences the efficiency of binding as well as the peptide transport specificity (67).
X
ABCB3 p.Ala374Asp 22700967:188:13
status: NEW209 It has been shown that A374D alters the peptide transport specificity (67).
X
ABCB3 p.Ala374Asp 22700967:209:23
status: NEW189 The mutation A374D in human TAP2 influences the efficiency of binding as well as the peptide transport specificity (67).
X
ABCB3 p.Ala374Asp 22700967:189:13
status: NEW210 It has been shown that A374D alters the peptide transport specificity (67).
X
ABCB3 p.Ala374Asp 22700967:210:23
status: NEW[hide] Transporters associated with antigen processing (T... Dev Comp Immunol. 2011 Nov;35(11):1173-81. Epub 2011 Apr 19. Pinto RD, Pereira PJ, dos Santos NM
Transporters associated with antigen processing (TAP) in sea bass (Dicentrarchus labrax, L.): molecular cloning and characterization of TAP1 and TAP2.
Dev Comp Immunol. 2011 Nov;35(11):1173-81. Epub 2011 Apr 19., [PMID:21540052]
Abstract [show]
The transporters associated with antigen processing (TAP), play an important role in the MHC class I antigen presentation pathway. In this work, sea bass (Dicentrarchus labrax) TAP1 and TAP2 genes and transcripts were isolated and characterized. Only the TAP2 gene is structurally similar to its human orthologue. As other TAP molecules, sea bass TAP1 and TAP2 are formed by one N-terminal accessory domain, one core membrane-spanning domain and one canonical C-terminal nucleotide-binding domain. Homology modelling of the sea bass TAP dimer predicts that its quaternary structure is in accordance with that of other ABC transporters. Phylogenetic analysis segregates sea bass TAP1 and TAP2 into each subfamily cluster of transporters, placing them in the fish class and suggesting that the basic structure of these transport-associated proteins is evolutionarily conserved. Furthermore, the present data provides information that will enable more studies on the class I antigen presentation pathway in this important fish species.
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No. Sentence Comment
139 In human TAP2, a single amino acid substitution (A374D), changes the preference for the transported peptide (Armandola et al., 1996).
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ABCB3 p.Ala374Asp 21540052:139:49
status: NEW[hide] Function of the transport complex TAP in cellular ... Biochim Biophys Acta. 1999 Dec 6;1461(2):405-19. Abele R, Tampe R
Function of the transport complex TAP in cellular immune recognition.
Biochim Biophys Acta. 1999 Dec 6;1461(2):405-19., [PMID:10581370]
Abstract [show]
The transporter associated with antigen processing (TAP) is essential for peptide loading onto major histocompatibility complex (MHC) class I molecules by translocating peptides into the endoplasmic reticulum. The MHC-encoded ABC transporter works in concert with the proteasome and MHC class I molecules for the antigen presentation on the cell surface for T cell recognition. TAP forms a heterodimer where each subunit consists of a hydrophilic nucleotide binding domain and a hydrophobic transmembrane domain. The transport mechanism is a multistep process composed of an ATP-independent peptide association step which induces a structural reorganization of the transport complex that may trigger the ATP-driven transport of the peptide into the endoplasmic reticulum lumen. By using combinatorial peptide libraries, the substrate selectivity and the recognition principle of TAP have been elucidated. TAP maximizes the degree of substrate diversity in combination with high substrate affinity. This ABC transporter is also unique as it is closely associated with chaperone-like proteins involved in bonding of the substrate onto MHC molecules. Most interestingly, virus-infected and malignant cells have developed strategies to escape immune surveillance by affecting TAP expression or function.
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No. Sentence Comment
352 Moreover, two pairs of residues (217/218) and (374/ 380) of rat TAP and a single point mutation (A374D) of human TAP a¡ect the substrate speci'city [78,80].
X
ABCB3 p.Ala374Asp 10581370:352:97
status: NEW[hide] Functional analysis by site-directed mutagenesis o... J Immunol. 1998 Mar 15;160(6):2767-79. Deverson EV, Leong L, Seelig A, Coadwell WJ, Tredgett EM, Butcher GW, Howard JC
Functional analysis by site-directed mutagenesis of the complex polymorphism in rat transporter associated with antigen processing.
J Immunol. 1998 Mar 15;160(6):2767-79., [PMID:9510178]
Abstract [show]
The transporter associated with Ag processing, TAP, is an endoplasmic reticulum resident heterodimeric member of the ATP-binding cassette transporter family. TAP transports short peptides from cytosol to the endoplasmic reticulum lumen for loading into recently synthesized class I MHC molecules. In the rat, two alleles of the TAP2 chain differ in their permissiveness to the transport of peptides with small hydrophobic, polar, or charged amino acids at the C terminus, and this correlates with differences between the peptide sets loaded into certain class I molecules in vivo. We have used segmental exchanges and site-directed mutagenesis to identify the residues in rat TAP2 responsible for differential transport between the two alleles of peptides terminating above all in the positively charged residue, arginine. Of the 25 residues by which the two functional TAP2 alleles differ, we have localized differential transport of peptides with a C-terminal arginine to two adjacent clusters of exchanges in the membrane domain involving a total of five amino acids. Each cluster, transferred by site-directed mutagenesis from the permissive to the restrictive sequence, can independently confer on TAP a partial ability to transport peptides with arginine at the C terminus. The results suggest that the permissive TAP2-A allele evolved in at least two steps, each partially permissive for peptides with charged C termini.
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No. Sentence Comment
300 In addition, a point mutation of human TAP2 residue 374 from alanine to aspartic acid resulted in some loss of permissiveness again, suggesting a significant role for this region (22).
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ABCB3 p.Ala374Asp 9510178:300:52
status: NEW