Article
Biochemistry & Molecular Biology
Md Rokonujjaman, Abdulrazak Sahyouni, Robert Wolfe, Lihui Jia, Ujjayini Ghosh, David P. Weliky
Summary: The study found that V2E mutation in HIV gp41 subunit attenuates fusion and infection mediated by HIV gp160. V2E also exhibits dominance in WT/V2E mixtures. V2E is located at the N-terminus of the fusion peptide (Fp), which binds the target membrane. The study also reveals that vesicle fusion induced by FP_HM, a large gp41 ectodomain construct, shows significant attenuation and dominance with V2E.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sai Chaitanya Chiliveri, John M. Louis, Robert B. Best, Ad Bax
Summary: This study measured the dynamic equilibrium of the HIV-1 virus envelope glycoprotein gp41 in the presence of lipid mimics and determined the reaction kinetics and energy associated with its lipid-bound intermediate and post-fusion six-helical bundle states. The findings provide important insights into the molecular basis of viral membrane fusion.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biology
Christophe Caillat, Delphine Guilligay, Johana Torralba, Nikolas Friedrich, Jose L. Nieva, Alexandra Trkola, Christophe J. Chipot, Francois L. Dehez, Winfried Weissenhorn
Summary: The study presents the crystal structure of HIV-1 gp41 locked in a fusion intermediate state by a neutralizing antibody, showing the structural plasticity and conformational flexibility of membrane anchors. Molecular dynamics simulation suggests a possible transition pathway into the final post-fusion conformation, highlighting the potential of MPER-specific broadly neutralizing antibodies to block membrane fusion.
Article
Multidisciplinary Sciences
Igor de la Arada, Johana Torralba, Igor Tascon, Adai Colom, Iban Ubarretxena-Belandia, Jose L. R. Arrondo, Beatriz Apellaniz, Jose L. Nieva
Summary: Envelope glycoproteins from genetically-divergent virus families contain fusion peptides that can insert into and disrupt target cell membranes during virus-cell fusion. Membrane-proximal external regions (MPERs) have been implicated in promoting the viral membrane restructuring event required for fusion, but it is unclear whether the structure-function relationships governing canonical fusion peptides also apply to MPER sequences.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Li He, Guangyan Zhou, Vladimir Sofiyev, Eddie Garcia, Newton Nguyen, Kathy H. H. Li, Miriam Gochin
Summary: The study investigates the conversion of molecules with better drug-like properties to improve antiviral efficacy. By adding an electrophilic warhead, equilibrium binders can be converted into inhibitors. This method shows promise in inhibiting HIV-1 entry.
Article
Biochemistry & Molecular Biology
Daniel Birtles, Anna E. Oh, Jinwoo Lee
Summary: The fusion domain of SARS-CoV-2 spike glycoprotein consists of a fusion peptide and a fusion loop, and it can initiate membrane fusion at both plasma and endosomal membranes. The fusion ability of the fusion domain is more prominent at a lower pH, with a preference for initiating fusion at the late endosome membrane. The integrity of the disulfide bond and hydrophobic motif LLF within the fusion domain is crucial for its function.
Article
Chemistry, Multidisciplinary
Sai Chaitanya Chiliveri, John M. Louis, Ad Bax
Summary: The membrane proximal external region (MPER) of HIV-1 gp41 contains epitopes for at least four broadly neutralizing antibodies. In aqueous solution, the MPER fragment exists in a monomer-trimer equilibrium with exothermic association, more favorable in D2O than H2O, and increasing with ionic strength. Structural transition of MPER from unfolded monomer to alpha-helical trimer has implications for antibody recognition.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Remigiusz Worch, Anita Dudek, Paulina Borkowska, Piotr Setny
Summary: The fusion of viral and host cell membranes is a critical step in the life cycle of enveloped viruses. Studies have shown that subunit 2 of hemagglutinin glycoprotein mediates fusion, and fusion peptides possess fusogenic activity, but their mechanism of action remains unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yue Hu, Wenjiang Yu, Xiuzhu Geng, Yuanmei Zhu, Huihui Chong, Yuxian He
Summary: In this study, we investigated the effect of C16 modification on the resistance barrier of the inhibitor LP-40. The results showed that the LP-40 activity is enhanced and that it has a high resistance barrier. LP-40 and T20 have similar resistance mutation sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhonghua Ji, Bingying Lin, Enshuang Guan, Mingsen Zhou, Hui Wang, Ying Hu
Summary: Melanoma, the deadliest type of skin cancer, has seen significant improvement in patient survival through anti-tumor immunotherapy. However, physiological barriers hinder drug bioavailability. Cell membranes, such as B16F10 cell membranes (BFMs), have emerged as promising drug delivery vehicles. In this study, BFMs acted as both antigens and vesicles for vaccines, overcoming immune tolerance by being taken up by dendritic cells (DCs) and combined with adjuvants. WT-modified BFMs (WT-BFMs) coated with F127-PTX showed enhanced cellular uptake and elicited robust immune responses.
Article
Biochemistry & Molecular Biology
Nhi Tran, Younghoon Oh, Madeleine Sutherland, Qiang Cui, Mei Hong
Summary: Recent research using solid-state NMR spectroscopy and molecular dynamics simulations has found that the MPER-TMD trimers of gp41, the fusion protein component of HIV-1 envelope glycoprotein, cluster in membranes with high cholesterol content, and cholesterol may affect gp41 clustering by indirectly modulating the orientation of MPER.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biophysics
Maria Elena Tarnok, Fanny Guzman, Luis F. Aguilar
Summary: This study investigated the influence of cholesterol content on membrane fusion facilitated by ISAV fusion peptides. Results showed that cholesterol affected membrane fusion, but the peptides did not require cholesterol in their membranes for fusion in the smallest lipid vesicles (0.2 μm LUV).
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Chemistry, Medicinal
Wei Xu, Zhe Cong, Qianyu Duan, Qian Wang, Shan Su, Rui Wang, Lu Lu, Jing Xue, Shibo Jiang
Summary: A protein-based, long-acting HIV fusion inhibitor called FLT was designed and constructed, which binds with human serum albumin in a reversible manner to prolong the half-life of the HIV fusion inhibitor T1144. FLT showed high efficiency in inhibiting HIV infection and is considered a promising candidate for a new protein-based anti-HIV drug.
Article
Chemistry, Multidisciplinary
Ye Zeng, Mengjie Shen, Ankush Singhal, Geert Jan Agur Sevink, Niek Crone, Aimee L. L. Boyle, Alexander Kros
Summary: An ideal nanomedicine system improves drug therapy by enhancing cellular uptake. However, current nanomedicines mainly enter cells through endosomal/lysosomal pathways, leading to inefficient delivery of therapeutic cargo. To overcome this issue, the authors developed a synthetic lipidated peptide pair, E4/K4, inspired by natural fusion machinery. By optimizing the structure of the peptide, the researchers achieved enhanced membrane fusion and efficient delivery of drugs into cells. This study provides valuable insights for the development of efficient drug delivery systems based on liposome-cell fusion strategies.
Article
Biochemistry & Molecular Biology
Mario Cano-Munoz, Julie Lucas, Li-Yun Lin, Samuele Cesaro, Christiane Moog, Francisco Conejero-Lara
Summary: This study identified the vulnerability of the gp41 C-terminal heptad repeat to inhibition and demonstrated that engineering stable miniproteins can enhance inhibitory potency against HIV-1. These findings have implications in the development of new strategies to inhibit HIV targeting the gp41 CHR region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Uwe Schlattner, Malgorzata Tokarska-Schlattner, Richard M. Epand, Mathieu Boissan, Marie-Lise Lacombe, Valerian E. Kagan
LABORATORY INVESTIGATION
(2018)
Article
Biochemistry & Molecular Biology
Tomohiro Kimura, Atsuko K. Kimura, Mindong Ren, Bob Berno, Yang Xu, Michael Schlame, Richard M. Epand
Article
Biochemistry & Molecular Biology
Jose Carlos Bozelli, William Jennings, Stephanie Black, Yu Heng Hou, Darius Lameire, Preet Chatha, Tomohiro Kimura, Bob Berno, Adree Khondker, Maikel C. Rheinstadter, Richard M. Epand
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Review
Biochemistry & Molecular Biology
Jose Carlos Bozelli, Richard M. Epand
CHEMISTRY AND PHYSICS OF LIPIDS
(2019)
Review
Biochemical Research Methods
Jose Carlos Bozelli, Richard M. Epand
Article
Biochemistry & Molecular Biology
Jose Carlos Bozelli, Yu H. Hou, Shirley Schreier, Richard M. Epand
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Jose Carlos Bozelli, Daniel Lu, G. Ekin Atilla-Gokcumen, Richard M. Epand
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2020)
Review
Biochemistry & Molecular Biology
William Jennings, Richard M. Epand
CHEMISTRY AND PHYSICS OF LIPIDS
(2020)
Review
Biochemistry & Molecular Biology
Jose Carlos Bozelli, Richard M. Epand
BIOPHYSICAL CHEMISTRY
(2020)
Review
Endocrinology & Metabolism
Jose Carlos Bozelli, Richard M. Epand
Summary: Barth syndrome is a rare inherited metabolic disease caused by mutations in the gene of the enzyme tafazzin, leading to abnormalities in mitochondrial-specific lipid cardiolipin (CL) and plasmalogens. The molecular mechanism linking CL and plasmalogens is not fully understood, but there is evidence of interplay between the two lipid species in BTHS. Therapeutic approaches targeting the regulation of plasmalogens are being discussed as potential new treatments for BTHS.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Polymer Science
Derrick E. Hastings, Jose C. Bozelli, Richard M. Epand, Harald D. H. Stover
Summary: The transition from self-coacervation to complex coacervation of a series of charge-balanced polyampholyte (PA) and polyelectrolyte (PE) pairs based on copolymers of methacrylic acid and N-(3-aminopropyl) methacrylamide hydrochloride was described, focusing on the effects of charge distribution on coacervate properties. The study found that higher molecular weight complex coacervates exhibited increased resistance to stimuli such as ionic strength and pH, compared to liquid self-coacervates and less hydrated coacervates formed from two PE homopolymers with complementary nonstoichiometric PAs.
Review
Biochemistry & Molecular Biology
Jose Carlos Bozelli, Richard M. Epand
Summary: Plasmalogens, a subclass of glycerophospholipids, have been found to play a crucial role in various pathological conditions. Plasmalogen replacement therapy (PRT) has shown promising results in restoring plasmalogen levels and ameliorating disease phenotype. The focus on lipids as therapeutic targets presents a modern and innovative approach in molecular medicine for improving health outcomes in clinically unmet needs.
Article
Chemistry, Physical
Sukhvershjit S. Aulakh, Jose Carlos Bozelli Jr, Richard M. Epand
Summary: In this study, the properties of all 10 human DGK paralogs were comprehensively investigated using the protein structural prediction technology Alphafold 2.0. The predictions revealed conserved structural features and provided insights into the functional properties of DGK. The existence of a conserved ATP-binding site and energetically favorable interaction with curved membranes were also discovered.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biology
Tomohiro Kimura, Atsuko K. Kimura, Mindong Ren, Vernon Monteiro, Yang Xu, Bob Berno, Michael Schlame, Richard M. Epand
LIFE SCIENCE ALLIANCE
(2019)
Article
Chemistry, Multidisciplinary
Rashik Ahmed, Michael Akcan, Adree Khondker, Maikel C. Rheinstadter, Jose C. Bozelli, Richard M. Epand, Vincent Huynh, Ryan G. Wylie, Stephen Boulton, Jinfeng Huang, Chris P. Verschoor, Giuseppe Melacini
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)