ABCG2 p.Val556Ser
| Predicted by SNAP2: | A: D (71%), C: D (66%), D: D (91%), E: D (85%), F: D (75%), G: D (85%), H: D (85%), I: N (53%), K: D (91%), L: N (53%), M: D (75%), N: D (80%), P: D (91%), Q: D (80%), R: D (85%), S: D (80%), T: D (80%), W: D (91%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Towards understanding the mechanism of action of t... J Mol Graph Model. 2007 Mar;25(6):837-51. Epub 2006 Aug 30. Li YF, Polgar O, Okada M, Esser L, Bates SE, Xia D
Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study.
J Mol Graph Model. 2007 Mar;25(6):837-51. Epub 2006 Aug 30., [PMID:17027309]
Abstract [show]
The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1-3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal beta-strand (S6) of the central beta-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD.
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No. Sentence Comment
204 To test these possibilities, we made two mutants, F431S and V556S, and probed cell surface expression with the ABCG2 specific monoclonal antibody 5D3 [39] (Fig. 5A).
X
ABCG2 p.Val556Ser 17027309:204:60
status: VERIFIED206 Flow cytometry analysis of ABCG2 mutants F431S and V556S.
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ABCG2 p.Val556Ser 17027309:206:51
status: VERIFIED207 (A) Using the 5D3 surface antibody, the F431S and V556S mutant proteins are detectable on the cell surface of HEK293 cells.
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ABCG2 p.Val556Ser 17027309:207:50
status: VERIFIED219 In particular, the residue V556 in the final model faces G498 in the TM3 helix of the neighboring subunit, explaining the phenotype for the V556S mutant because it faces a small residue.
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ABCG2 p.Val556Ser 17027309:219:140
status: VERIFIED