{"entity": "researcher", "timestamp": "2026-07-20T00:58:14.992Z", "family": "Nomura", "given": "Norimichi", "initials": "N", "orcid": "0000-0002-6330-2239", "affiliations": ["Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/2b604af54f4a49f8a7884fbd70d99101.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/2b604af54f4a49f8a7884fbd70d99101"}}, "publications": [{"entity": "publication", "iuid": "ef64425174314a07beeabf70289268e4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef64425174314a07beeabf70289268e4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef64425174314a07beeabf70289268e4"}}, "title": "Stepwise ATP translocation into the endoplasmic reticulum by human SLC35B1.", "authors": [{"family": "Gulati", "given": "Ashutosh", "initials": "A", "orcid": "0000-0003-0960-994X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0b2b0aa7260492c8141083762e08125.json"}}, {"family": "Ahn", "given": "Do-Hwan", "initials": "DH", "orcid": "0009-0007-1596-5621", "researcher": {"href": "https://publications.scilifelab.se/researcher/e261a6911b7441259e69545e2dfa2d1f.json"}}, {"family": "Suades", "given": "Albert", "initials": "A"}, {"family": "Hult", "given": "Yurie", "initials": "Y"}, {"family": "Wolf", "given": "Gernot", "initials": "G"}, {"family": "Iwata", "given": "So", "initials": "S"}, {"family": "Superti-Furga", "given": "Giulio", "initials": "G", "orcid": "0000-0002-0570-1768", "researcher": {"href": "https://publications.scilifelab.se/researcher/792572f495f9444d8051c9767b601349.json"}}, {"family": "Nomura", "given": "Norimichi", "initials": "N", "orcid": "0000-0002-6330-2239", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b604af54f4a49f8a7884fbd70d99101.json"}}, {"family": "Drew", "given": "David", "initials": "D", "orcid": "0000-0001-8866-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc19844f8147480fb0af2e437744131b.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "643", "issue": "8072", "pages": "855-864", "issn-l": "0028-0836"}, "abstract": "ATP generated in the mitochondria is exported by an ADP/ATP carrier of the SLC25 family1. The endoplasmic reticulum (ER) cannot synthesize ATP but must import cytoplasmic ATP to energize protein folding, quality control and trafficking2,3. It was recently proposed that a member of the nucleotide sugar transporter family, termed SLC35B1 (also known as AXER), is not a nucleotide sugar transporter but a long-sought-after ER importer of ATP4. Here we report that human SLC35B1 does not bind nucleotide sugars but indeed executes strict ATP/ADP exchange with uptake kinetics consistent with the import of ATP into crude ER microsomes. A CRISPR-Cas9 cell-line knockout demonstrated that SLC35B1 clusters with the most essential SLC transporters for cell growth, consistent with its proposed physiological function. We have further determined seven cryogenic electron microscopy structures of human SLC35B1 in complex with an Fv fragment and either bound to an ATP analogue or ADP in all major conformations of the transport cycle. We observed that nucleotides were vertically repositioned up to approximately 6.5 \u00c5 during translocation while retaining key interactions with a flexible substrate-binding site. We conclude that SLC35B1 operates by a stepwise ATP translocation mechanism, which is a previously undescribed model for substrate translocation by an SLC transporter.", "doi": "10.1038/s41586-025-09069-w", "pmid": "40399679", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12267056"}, {"db": "pii", "key": "10.1038/s41586-025-09069-w"}], "notes": [], "created": "2025-11-23T22:21:14.741Z", "modified": "2025-11-23T22:21:15.218Z"}, {"entity": "publication", "iuid": "bebf3754bd684c6193cb41b10e65ba73", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bebf3754bd684c6193cb41b10e65ba73.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bebf3754bd684c6193cb41b10e65ba73"}}, "title": "Structure and Inhibition of the Human Na+/H+ Exchanger SLC9B2.", "authors": [{"family": "Jung", "given": "Sukkyeong", "initials": "S"}, {"family": "Kokane", "given": "Surabhi", "initials": "S"}, {"family": "Li", "given": "Hang", "initials": "H"}, {"family": "Iwata", "given": "So", "initials": "S"}, {"family": "Nomura", "given": "Norimichi", "initials": "N", "orcid": "0000-0002-6330-2239", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b604af54f4a49f8a7884fbd70d99101.json"}}, {"family": "Drew", "given": "David", "initials": "D", "orcid": "0000-0001-8866-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc19844f8147480fb0af2e437744131b.json"}}], "type": "journal article", "published": "2025-04-29", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "26", "issue": "9", "issn-l": null}, "abstract": "The sodium/proton exchanger NHA2, also known as SLC9B2, is important for insulin secretion, renal blood pressure regulation, and electrolyte retention. Recent structures of bison NHA2 has revealed its unique 14-transmembrane helix architecture, which is different from SLC9A/NHE members made up from 13-TM helices. Sodium/proton exchangers are functional homodimers, and the additional N-terminal helix in NHA2 was found to alter homodimer assembly. Here, we present the cryo-electron microscopy structures of apo human NHA2 in complex with a Fab fragment and also with the inhibitor phloretin bound at 2.8 and 2.9 \u00c5 resolution, respectively. We show how phosphatidic acid (PA) lipids bind to the homodimer interface of NHA2 on the extracellular side, which we propose has a regulatory role linked to cell volume regulation. The ion binding site of human NHA2 has a salt bridge interaction between the ion binding aspartate D278 and R432, an interaction previously broken in the bison NHA2 structure, and these differences suggest a possible ion coupling mechanism. Lastly, the human NHA2 structure in complex with phloretin offers a template for structure-guided drug design, potentially leading to the development of more selective and potent NHA2 inhibitors.", "doi": "10.3390/ijms26094221", "pmid": "40362458", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12072577"}, {"db": "pii", "key": "ijms26094221"}], "notes": [], "created": "2025-11-23T22:22:48.254Z", "modified": "2025-11-23T22:22:48.286Z"}, {"entity": "publication", "iuid": "16948fd9c1e947eab8b9487a32da850b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/16948fd9c1e947eab8b9487a32da850b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/16948fd9c1e947eab8b9487a32da850b"}}, "title": "Structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2.", "authors": [{"family": "Matsuoka", "given": "Rei", "initials": "R"}, {"family": "Fudim", "given": "Roman", "initials": "R", "orcid": "0000-0001-5101-3184", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0ffbe654828498d90ebcfeac084a082.json"}}, {"family": "Jung", "given": "Sukkyeong", "initials": "S", "orcid": "0000-0002-4730-5245", "researcher": {"href": "https://publications.scilifelab.se/researcher/f65f769bad8a4fd6a4186b7ddaaf6051.json"}}, {"family": "Zhang", "given": "Chenou", "initials": "C"}, {"family": "Bazzone", "given": "Andre", "initials": "A", "orcid": "0000-0002-2419-3519", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c714875986841b788d700b56f4f093c.json"}}, {"family": "Chatzikyriakidou", "given": "Yurie", "initials": "Y"}, {"family": "Robinson", "given": "Carol V", "initials": "CV", "orcid": "0000-0001-7829-5505", "researcher": {"href": "https://publications.scilifelab.se/researcher/109418b5455b4a32bcff02b54d49885b.json"}}, {"family": "Nomura", "given": "Norimichi", "initials": "N", "orcid": "0000-0002-6330-2239", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b604af54f4a49f8a7884fbd70d99101.json"}}, {"family": "Iwata", "given": "So", "initials": "S", "orcid": "0000-0003-1735-2937", "researcher": {"href": "https://publications.scilifelab.se/researcher/dadeb06908fa4d679e2b5344a4484c0d.json"}}, {"family": "Landreh", "given": "Michael", "initials": "M", "orcid": "0000-0002-7958-4074", "researcher": {"href": "https://publications.scilifelab.se/researcher/87494f4204c04be9bce5e9ddcdc92d8a.json"}}, {"family": "Orellana", "given": "Laura", "initials": "L"}, {"family": "Beckstein", "given": "Oliver", "initials": "O", "orcid": "0000-0003-1340-0831", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ebdd85d6b214b78bdd2d13df4822ba0.json"}}, {"family": "Drew", "given": "David", "initials": "D", "orcid": "0000-0001-8866-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc19844f8147480fb0af2e437744131b.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Nat. Struct. Mol. Biol.", "issn": "1545-9985", "volume": "29", "issue": "2", "pages": "108-120", "issn-l": "1545-9985"}, "abstract": "The Na+/H+ exchanger SLC9B2, also known as NHA2, correlates with the long-sought-after Na+/Li+ exchanger linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Despite the functional importance of NHA2, structural information and the molecular basis for its ion-exchange mechanism have been lacking. Here we report the cryo-EM structures of bison NHA2 in detergent and in nanodiscs, at 3.0 and 3.5 \u00c5 resolution, respectively. The bison NHA2 structure, together with solid-state membrane-based electrophysiology, establishes the molecular basis for electroneutral ion exchange. NHA2 consists of 14 transmembrane (TM) segments, rather than the 13 TMs previously observed in mammalian Na+/H+ exchangers (NHEs) and related bacterial antiporters. The additional N-terminal helix in NHA2 forms a unique homodimer interface with a large intracellular gap between the protomers, which closes in the presence of phosphoinositol lipids. We propose that the additional N-terminal helix has evolved as a lipid-mediated remodeling switch for the regulation of NHA2 activity.", "doi": "10.1038/s41594-022-00738-2", "pmid": "35173351", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8850199"}, {"db": "pii", "key": "10.1038/s41594-022-00738-2"}], "notes": [], "created": "2023-11-24T18:05:36.006Z", "modified": "2023-11-24T18:05:36.279Z"}]}