Cryo-EM structure of a nanobody-bound heliorhodopsin

Ruixue Xia; Mingxia Sun; Yang Lu; Na Wang; Anqi Zhang; Changyou Guo; Zhenmei Xu; Xuehui Cai; Yuanzheng He

doi:10.1016/j.bbrc.2025.151398

Cryo-EM structure of a nanobody-bound heliorhodopsin

Ruixue Xia
, Mingxia Sun
, Yang Lu
, Na Wang
, Anqi Zhang
, Changyou Guo
, Zhenmei Xu^*
, Xuehui Cai^*
, Yuanzheng He^*

^*Corresponding author for this work

Faculty of Life Sciences and Medicine

School of Life Science and Technology, Harbin Institute of Technology
Chinese Academy of Agricultural Sciences

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Heliorhodopsins (HeRs) represent a distinct class of microbial rhodopsins (MRs) with an inverted membrane topology compared to other MRs. Previous structural studies have shown that HeRs lack a proton acceptor residue, and protons are never released from the protein. In this study, we present the cryo-electron microscopy (cryo-EM) structure of HeR bound to a nanobody. The structure reveals an acetate-like molecule in the Schiff base cavity (SBC) on the intracellular side of HeR under neutral condition. Structural comparisons and analyses suggest that the acetate molecule may function as a proton acceptor for the protonated retinal Schiff base (RSB) and act as a mediator for the intramolecular signaling transduction in HeR during light stimulation. These structural insights shed new light on the mechanism and function of HeR.

Original language	English
Article number	151398
Journal	Biochemical and Biophysical Research Communications
Volume	750
DOIs	https://doi.org/10.1016/j.bbrc.2025.151398
State	Published - 1 Mar 2025

Keywords

Acetate
Cryo-EM
Heliorhodopsin
Nanobody

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10.1016/j.bbrc.2025.151398

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title = "Cryo-EM structure of a nanobody-bound heliorhodopsin",

abstract = "Heliorhodopsins (HeRs) represent a distinct class of microbial rhodopsins (MRs) with an inverted membrane topology compared to other MRs. Previous structural studies have shown that HeRs lack a proton acceptor residue, and protons are never released from the protein. In this study, we present the cryo-electron microscopy (cryo-EM) structure of HeR bound to a nanobody. The structure reveals an acetate-like molecule in the Schiff base cavity (SBC) on the intracellular side of HeR under neutral condition. Structural comparisons and analyses suggest that the acetate molecule may function as a proton acceptor for the protonated retinal Schiff base (RSB) and act as a mediator for the intramolecular signaling transduction in HeR during light stimulation. These structural insights shed new light on the mechanism and function of HeR.",

keywords = "Acetate, Cryo-EM, Heliorhodopsin, Nanobody",

author = "Ruixue Xia and Mingxia Sun and Yang Lu and Na Wang and Anqi Zhang and Changyou Guo and Zhenmei Xu and Xuehui Cai and Yuanzheng He",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Inc.",

year = "2025",

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doi = "10.1016/j.bbrc.2025.151398",

language = "英语",

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journal = "Biochemical and Biophysical Research Communications",

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T1 - Cryo-EM structure of a nanobody-bound heliorhodopsin

AU - Xia, Ruixue

AU - Sun, Mingxia

AU - Lu, Yang

AU - Wang, Na

AU - Zhang, Anqi

AU - Guo, Changyou

AU - Xu, Zhenmei

AU - Cai, Xuehui

AU - He, Yuanzheng

PY - 2025/3/1

Y1 - 2025/3/1

N2 - Heliorhodopsins (HeRs) represent a distinct class of microbial rhodopsins (MRs) with an inverted membrane topology compared to other MRs. Previous structural studies have shown that HeRs lack a proton acceptor residue, and protons are never released from the protein. In this study, we present the cryo-electron microscopy (cryo-EM) structure of HeR bound to a nanobody. The structure reveals an acetate-like molecule in the Schiff base cavity (SBC) on the intracellular side of HeR under neutral condition. Structural comparisons and analyses suggest that the acetate molecule may function as a proton acceptor for the protonated retinal Schiff base (RSB) and act as a mediator for the intramolecular signaling transduction in HeR during light stimulation. These structural insights shed new light on the mechanism and function of HeR.

AB - Heliorhodopsins (HeRs) represent a distinct class of microbial rhodopsins (MRs) with an inverted membrane topology compared to other MRs. Previous structural studies have shown that HeRs lack a proton acceptor residue, and protons are never released from the protein. In this study, we present the cryo-electron microscopy (cryo-EM) structure of HeR bound to a nanobody. The structure reveals an acetate-like molecule in the Schiff base cavity (SBC) on the intracellular side of HeR under neutral condition. Structural comparisons and analyses suggest that the acetate molecule may function as a proton acceptor for the protonated retinal Schiff base (RSB) and act as a mediator for the intramolecular signaling transduction in HeR during light stimulation. These structural insights shed new light on the mechanism and function of HeR.

KW - Acetate

KW - Cryo-EM

KW - Heliorhodopsin

KW - Nanobody

UR - https://www.scopus.com/pages/publications/85216296203

U2 - 10.1016/j.bbrc.2025.151398

DO - 10.1016/j.bbrc.2025.151398

M3 - 文章

C2 - 39889627

AN - SCOPUS:85216296203

SN - 0006-291X

VL - 750

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

M1 - 151398

ER -

Cryo-EM structure of a nanobody-bound heliorhodopsin

Abstract

Keywords

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