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Structural and Functional Insights into Membrane Transporters: A Tribute to Dr. Ernest Wright

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 455

Special Issue Editor


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Guest Editor
Department of Physiology, School of Medicine, University of California, Los Angeles, CA 90095, USA
Interests: transporters; channnbels; biophysics; crystallography; cryo-EM

Special Issue Information

Dear Colleagues,

This Special Issue will commemorate the outstanding career of Dr. Ernest Wright, who has recently retired. Dr. Wright, a member of both the Royal Society and the National Academy of Sciences, is renowned for his pioneering contributions to the field of membrane transport, particularly in the cloning and characterization of sodium-glucose co-transporters (SGLTs). His groundbreaking discoveries have shaped our understanding of glucose transport and its implications for human health, laying the foundation for therapeutic advances in diabetes and cancer treatment.

This Special Issue will take a broader approach to membrane transporters, examining various classes of transporters and exploring their structural and functional relationships, as well as their roles in health and disease. By bringing together cutting-edge research, this Special Issue will provide a comprehensive overview of how membrane transporters contribute to cellular function and how their dysfunction can lead to disease.

It is our honor to celebrate Dr. Wright’s illustrious career with this collection of studies, which will also inspire future research in the field of membrane transport.

Prof. Dr. Jeff Abramson
Guest Editor

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Keywords

  • membrane transporters
  • membrane protein
  • glucose transport
  • cell membrane
  • interface reaction

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Published Papers (1 paper)

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Research

20 pages, 3317 KiB  
Article
Structure and Inhibition of the Human Na+/H+ Exchanger SLC9B2
by Sukkyeong Jung, Surabhi Kokane, Hang Li, So Iwata, Norimichi Nomura and David Drew
Int. J. Mol. Sci. 2025, 26(9), 4221; https://doi.org/10.3390/ijms26094221 - 29 Apr 2025
Viewed by 130
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. [...] Read more.
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 Å 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. Full article
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