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TitleUnveiling Eukaryotic Membrane Proteins in High Resolution Using Peptide Solubilization.
Journal, issue, pagesJ Mol Biol, Vol. 437, Issue 24, Page 169467, Year 2025
Publish dateDec 15, 2025
AuthorsJiahe Zang / Yiting Shi / Weiyu Tao / Xiaoyu Liu / Wenjun Guo / Lei Chen /
PubMed AbstractIntegral membrane proteins are vital for numerous biological functions and their structures are typically studied using X-ray crystallography and cryo-electron microscopy (cryo-EM). However, these ...Integral membrane proteins are vital for numerous biological functions and their structures are typically studied using X-ray crystallography and cryo-electron microscopy (cryo-EM). However, these techniques require the extraction of target membrane proteins from their native membranes using detergents, which might disrupt the lipid environments and alter protein behavior. In this study, we present a novel method for solubilizing membrane proteins using 4F peptide, thereby eliminating the need for detergents throughout the procedure. We demonstrate that the 4F peptide effectively solubilizes a range of membrane proteins and complexes into 4F-discs, while preserving their functionality and structural integrity. Converting these 4F-discs into nanodiscs further enhances particle homogeneity and facilitates high-resolution structural determination of membrane proteins. Our findings highlight the potential of membrane-solubilizing peptides to advance membrane protein research.
External linksJ Mol Biol / PubMed:41061950
MethodsEM (single particle)
Resolution2.72 Å
Structure data

65025

9vfi

EMDB-65025, PDB-9vfi:
Structure of hTRPC3 solubilized with 4F peptide at 2.72 angstrom
Method: EM (single particle) / Resolution: 2.72 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-ZN:
Unknown entry

PDB-1l5i:
30-CONFORMER NMR ENSEMBLE OF THE N-TERMINAL, DNA-BINDING DOMAIN OF THE REPLICATION INITIATION PROTEIN FROM A GEMINIVIRUS (TOMATO YELLOW LEAF CURL VIRUS-SARDINIA)

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsMETAL TRANSPORT / TRPC3 / 4F peptide / native lipid environment

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