Pore-forming proteins (PFPs) are of special interest because of the association of their activity with the disruption of the membrane impermeability barrier and cell death. They generally convert from a monomeric, soluble form into transmembrane oligomers that induce the opening of membrane pores. The study of pore formation in membranes with molecular detail remains a challenging endeavor because of its highly dynamic and complex nature, usually involving diverse oligomeric structures with different functionalities. Here we discuss current methods applied for the structural and functional characterization of PFPs at the individual vesicle and cell level. We highlight how the development of high-resolution and single-molecule imaging techniques allows the analysis of the structural organization of protein oligomers and pore entities in lipid membranes.
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http://dx.doi.org/10.1016/j.sbi.2021.03.012 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hong Kong 999077, China.
CO mineralization, a process where CO reacts with minerals to form stable carbonates, presents a sustainable approach for CO sequestration and mitigation of global warming. While the crucial role of water in regulating CO mineralization efficiency is widely acknowledged, a comprehensive understanding of the underlying mechanisms remains elusive. This study employs a combined experimental and atomistic simulation approach to elucidate the intricate mechanisms governing moisture-driven carbonation kinetics of calcium-bearing minerals.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Central European Institute of Technology, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic.
Understanding the molecular mechanisms of pore formation is crucial for elucidating fundamental biological processes and developing therapeutic strategies, such as the design of drug delivery systems and antimicrobial agents. Although experimental methods can provide valuable information, they often lack the temporal and spatial resolution necessary to fully capture the dynamic stages of pore formation. In this study, we present two novel collective variables (CVs) designed to characterize membrane pore behavior, particularly its energetics, through molecular dynamics (MD) simulations.
View Article and Find Full Text PDFCells
December 2024
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
Podocytes express large-conductance Ca-activated K channels (BK channels) and at least two different pore-forming KCa1.1 subunit C-terminal splice variants, known as VEDEC and EMVYR, along with auxiliary β and γ subunits. Podocyte KCa1.
View Article and Find Full Text PDFEMBO Rep
January 2025
Killer Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Cytotoxic lymphocytes are crucial to our immune system, primarily eliminating virus-infected or cancerous cells via perforin/granzyme killing. Perforin forms transmembrane pores in the plasma membrane, allowing granzymes to enter the target cell cytosol and trigger apoptosis. The prowess of cytotoxic lymphocytes to efficiently eradicate target cells has been widely harnessed in immunotherapies against haematological cancers.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, China.
Pyroptosis is a form of programmed cell death triggered by inflammatory caspases, dependent on the gasdermin (GSDM) family proteins forming membrane pores in the plasma membrane, with GSDM proteins serving as the executors of pyroptosis. This process can activate a robust inflammatory response through a cascade effect. Sepsis-associated acute kidney injury (SA-AKI) is a classical inflammatory disease with no specific therapeutic drug available.
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