RESUMEN
Pore-forming protein toxins (PFTs) represent a diverse class of membrane-damaging proteins that are produced by a wide variety of organisms. PFT-mediated membrane perforation is largely governed by the chemical composition and the physical properties of the plasma membranes. The interaction between the PFTs with the target membranes is critical for the initiation of the pore-formation process, and can lead to discrete membrane reorganization events that further aids in the process of pore-formation. Punching holes on the plasma membranes by the PFTs interferes with the cellular homeostasis by disrupting the ion-balance inside the cells that in turn can turn on multiple signalling cascades required to restore membrane integrity and cellular homeostasis. In this review, we discuss the physicochemical attributes of the plasma membranes associated with the pore-formation processes by the PFTs, and the subsequent membrane remodelling events that may start off the membrane-repair mechanisms.
Asunto(s)
Toxinas Biológicas , Membrana Celular/metabolismo , Membranas , Proteínas Citotóxicas Formadoras de Poros/química , Toxinas Biológicas/metabolismoRESUMEN
Pore-forming proteins/toxins (PFPs/PFTs) are the distinct class of membrane-damaging proteins. They act by forming oligomeric pores in the plasma membranes. PFTs and PFPs from diverse organisms share a common mechanism of action, in which the designated pore-forming motifs of the membrane-bound protein molecules insert into the membrane lipid bilayer to create the water-filled pores. One common characteristic of these pore-forming motifs is that they are amphipathic in nature. In general, the hydrophobic sidechains of the pore-forming motifs face toward the hydrophobic core of the membranes, while the hydrophilic residues create the lining of the water-filled pore lumen. Interestingly, pore-forming motifs of the distinct subclass of PFPs/PFTs share very little sequence similarity with each other. Therefore, the common guiding principle that governs the sequence-to-structure paradigm in the mechanism of action of these PFPs/PFTs still remains an enigma. In this article, we discuss this notion using the examples of diverse groups of membrane-damaging PFPs/PFTs.
Asunto(s)
Secuencia de Aminoácidos , Variación Genética , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/genética , Toxinas Biológicas/química , Toxinas Biológicas/genética , Animales , Membrana Celular/química , Membrana Celular/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Relación Estructura-Actividad , Toxinas Biológicas/metabolismoRESUMEN
Pore-forming toxins (PFTs) rupture plasma membranes and kill target cells. PFTs are secreted as soluble monomers that undergo drastic structural rearrangements upon interacting with the target membrane and generate transmembrane oligomeric pores. A detailed understanding of the molecular mechanisms of the pore-formation process remains unclear due to limited structural insights regarding the transmembrane oligomeric pore states of the PFTs. However, recent advances in the field of cryo-electron microscopy (cryo-EM) have led to the high-resolution structure determination of the oligomeric pore forms of diverse PFTs. Here, we discuss the pore-forming mechanisms of various PFTs, specifically the mechanistic details contributed by the cryo-EM-based structural studies.