Substrate binding in the mitochondrial ADP/ATP carrier is a step-wise process guiding the structural changes in the transport cycle.

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cam.issuedOnline2022-06-23
dc.contributor.authorMavridou, Vasiliki
dc.contributor.authorKing, Martin
dc.contributor.authorTavoulari, Sotiria
dc.contributor.authorRuprecht, Jonathan
dc.contributor.authorPalmer, Shane M
dc.contributor.authorKunji, Edmund
dc.contributor.orcidMavridou, Vasiliki [0000-0002-1019-1256]
dc.contributor.orcidKing, Martin [0000-0001-6030-5154]
dc.contributor.orcidTavoulari, Sotiria [0000-0002-4263-8905]
dc.contributor.orcidRuprecht, Jonathan [0000-0002-1838-7245]
dc.contributor.orcidKunji, Edmund [0000-0002-0610-4500]
dc.date.accessioned2022-06-29T19:45:12Z
dc.date.available2022-06-29T19:45:12Z
dc.date.issued2022-06-23
dc.date.submitted2021-12-20
dc.date.updated2022-06-29T19:45:11Z
dc.description.abstractMitochondrial ADP/ATP carriers import ADP into the mitochondrial matrix and export ATP to the cytosol to fuel cellular processes. Structures of the inhibited cytoplasmic- and matrix-open states have confirmed an alternating access transport mechanism, but the molecular details of substrate binding remain unresolved. Here, we evaluate the role of the solvent-exposed residues of the translocation pathway in the process of substrate binding. We identify the main binding site, comprising three positively charged and a set of aliphatic and aromatic residues, which bind ADP and ATP in both states. Additionally, there are two pairs of asparagine/arginine residues on opposite sides of this site that are involved in substrate binding in a state-dependent manner. Thus, the substrates are directed through a series of binding poses, inducing the conformational changes of the carrier that lead to their translocation. The properties of this site explain the electrogenic and reversible nature of adenine nucleotide transport.
dc.identifier.doi10.17863/CAM.85911
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.others41467-022-31366-5
dc.identifier.other31366
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338498
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/57/1464
dc.subject/631/535
dc.subject/631/1647/2204
dc.subject/631/57/2283
dc.subject/631/80/642/333
dc.subject/9
dc.subject/82/80
dc.subject/82/83
dc.subject/101/47
dc.subject/119
dc.subjectarticle
dc.titleSubstrate binding in the mitochondrial ADP/ATP carrier is a step-wise process guiding the structural changes in the transport cycle.
dc.typeArticle
dcterms.dateAccepted2022-06-14
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
pubs.funder-project-idMRC (MC_UU_00015/1)
pubs.funder-project-idMRC (MC_UU_00028/2)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-022-31366-5
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