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
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
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
Kunyu Wang, Shijian Zhang, Eden P. P. Go, Haitao Ding, Wei Li Wang, Hanh T. T. Nguyen, John C. C. Kappes, Heather Desaire, Joseph Sodroski, Youdong Mao
Summary: Cryo-EM structures of HIV-1 Env trimers reveal an asymmetric conformation that serves as a default intermediate state during virus entry and antibody evasion. Cleaved and uncleaved Env trimers exhibit consistent yet distinct asymmetric conformations, with one smaller and two larger opening angles. The broken symmetry assists Env binding and the extension of the gp41 HR1 helical coiled-coil, facilitating virus fusion with the target cell membrane.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Chao Wang, Shuai Xia, Xinling Wang, Yue Li, Huan Wang, Rong Xiang, Qinwen Jiang, Qiaoshuai Lan, Ruiying Liang, Qing Li, Shanshan Huo, Lu Lu, Qian Wang, Fei Yu, Keliang Liu, Shibo Jiang
Summary: This study reveals a new approach for treating HIV-1 and human beta-coronavirus infections. The researchers found that a peptide called N3G is not only effective against HIV-1 infection, but also highly effective in inhibiting human beta-coronavirus infections. These findings provide a new strategy for developing broad-spectrum antiviral drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
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
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)
Review
Biochemistry & Molecular Biology
Deborah E. Shalev
Summary: Metal chelation plays an important role in providing structural stability and forming reactive centers in metalloproteins. Peptide-metal complexes, which exist in nature, offer a way to study protein binding regions and control experimental variables effectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
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
Immunology
Li Ou, Krishana Gulla, Andrea Biju, Daniel W. Biner, Tatsiana Bylund, Anita Changela, Steven J. Chen, Cheng-Yan Zheng, Nicole Cibelli, Angela R. Corrigan, Hongying Duan, Christopher A. Gonelli, Wing-Pui Kong, Cheng Cheng, Sijy O'Dell, Edward K. Sarfo, Andrew Shaddeau, Shuishu Wang, Alison Vinitsky, Yanhong Yang, Baoshan Zhang, Yaqiu Zhang, Richard A. Koup, Nicole A. Doria-Rose, Jason G. Gall, John R. Mascola, Peter D. Kwong
Summary: This study investigated the impact of varying linkers between FP8 and rTTHC in conjugate-vaccine immunogens. The results showed that linker length, hydrophilicity, and peptide-carrier stoichiometry had an effect on the immunogenicity of the conjugates, while several commonly used crosslinkers yielded similar serological results.
Article
Microbiology
Caelan E. Radford, Philipp Schommers, Lutz Gieselmann, Katharine H. D. Crawford, Bernadeta Dadonaite, Timothy C. Yu, Adam S. Dingens, Julie Overbaugh, Florian Klein, Jesse D. Bloom
Summary: Understanding the specificities of human serum antibodies that neutralize HIV can inform prevention and treatment strategies. A deep mutational scanning system was developed to measure the effects of mutations to HIV envelope on antibody neutralization. The study found that different polyclonal serum show neutralizing activity against HIV by targeting various epitopes, similar to characterized monoclonal antibodies. Mapping the specificity of neutralizing activity in polyclonal serum will help in evaluating anti-HIV immune responses for prevention strategies.
CELL HOST & MICROBE
(2023)
Article
Chemistry, Multidisciplinary
Ioanna Gkogka, Nicholas M. Glykos
Summary: In this study, a folding molecular dynamics simulation was performed to investigate the structural and dynamical properties of Peptide T. The simulation revealed that Peptide T is flexible and dynamic, with a preference for the formation of beta-turns. The results were validated by comparing with experimental NMR data, showing a reasonable agreement between experiment and simulation. This study demonstrates that peptide folding simulations can provide physically relevant structural characterization.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(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
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)