Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter.
Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter.
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DOI：
10.1038/ncomms6419
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发表时间：
2014-11-07
影响因子：
16.6
通讯作者：
Tampe, Robert
中科院分区：
文献类型：
--
作者：
Grossmann, Nina;Vakkasoglu, Ahmet S.;Hulpke, Sabine;Abele, Rupert;Gaudet, Rachelle;Tampe, Robert
The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the conserved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. Our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate. ABC systems are an important class of transporters involved in human pathologies for which the basis for transport remains poorly understood. Here the authors suggest a molecular basis for ATP-powered vectorial peptide export by the human transporter associated with antigen processing (TAP).
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影响因子：
64.8
作者：
Korkhov, Vladimir M.;Mireku, Samantha A.;Locher, Kaspar P.
通讯作者：
Locher, Kaspar P.
影响因子：
32.4
作者：
Koopmann, JO;Albring, J;Momburg, F
通讯作者：
Momburg, F
影响因子：
4.8
作者：
Chen, M;Abele, R;Tampé, R
通讯作者：
Tampé, R
影响因子：
2.9
作者：
Jones, Peter M.;George, Anthony M.
通讯作者：
George, Anthony M.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH