Multiple Pendants-Bearing Triglucosides for Membrane Protein Studies: Effects of Pendant Length and Number on Micelle Interior Hydration and Protein Stability
Membrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic-lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β<sub>2</sub>AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research.
Authors
- Bernadette Byrne (ORCID: https://orcid.org/0000-0001-9598-9832)
- Lan Guan (ORCID: https://orcid.org/0000-0002-2274-361X)
- Hong Sik Yun (ORCID: https://orcid.org/0000-0002-2187-6840)
- Pil Seok Chae (ORCID: https://orcid.org/0000-0003-1799-3304)
- Baoliang Lan
- Wonpil Im (ORCID: https://orcid.org/0000-0001-5642-6041)
- Hyemi Bae
- Aiman Sadaf (ORCID: https://orcid.org/0000-0002-8206-2082)
- Kristine Salomon (ORCID: https://orcid.org/0000-0003-2170-7147)
- Hajin Lee (ORCID: https://orcid.org/0000-0001-8564-0522)
- Seonghoon Kim (ORCID: https://orcid.org/0000-0002-0050-1054)
- Muhammad Ehsan (ORCID: https://orcid.org/0000-0002-4723-7924)
- Claus J. Løland (ORCID: https://orcid.org/0000-0002-1773-1446)
- Menebere Woubshete
- Xiangyu Liu (ORCID: https://orcid.org/0000-0002-4191-1914)
- Samantha Stanfield
Institutions
- Texas Tech University (US)
- University of Copenhagen (DK)
- Lehigh University (US)
- Laboratoire de Biologie Physico-Chimique des Protéines Membranaires (FR)
- Center for Life Sciences (CN)
- Hanyang University (KR)
- Imperial College London (GB)
- Texas Tech University Health Sciences Center (US)
- Tsinghua University (CN)
Publication Details
- Journal
- Biomacromolecules
- Published
- 2025-03-14
- DOI
- https://doi.org/10.1021/acs.biomac.5c00036
- Citations
- 1
- Primary Topic
- Lipid Membrane Structure and Behavior
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Research Foundation
- National Research Foundation of Korea
- Ministry of SMEs and Startups
- National Institutes of Health
- Korea Technology and Information Promotion Agency for SMEs