Pathogen surface protein interfaces

Pathogen surface protein interfaces are the structural regions where microbial proteins interact with host cell receptors, extracellular matrix components, or other pathogen-derived proteins to facilitate infection (Arkin et al., Nature Reviews Drug Discovery, 2014). These interfaces are fundamental to biological processes such as viral attachment and fusion, bacterial adhesion, and the evasion of the host immune system (Pizarro-Cerdá & Cossart, Cell, 2006). For instance, viral glycoproteins like the SARS-CoV-2 spike protein or the HIV-1 envelope complex rely on specific interfacial residues to bind host receptors like ACE2 or CD4, respectively (V'kovski et al., Nature Reviews Microbiology, 2021). In bacteria, surface proteins known as adhesins or MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) mediate attachment to host tissues, a prerequisite for colonization and biofilm formation (Foster, Nature Reviews Microbiology, 2019). Therapeutic strategies targeting these interfaces include monoclonal antibodies that sterically hinder binding and small-molecule inhibitors that stabilize non-functional conformations or occupy binding pockets. While highly effective, the primary challenge in targeting these interfaces is the rapid emergence of resistance due to the high mutation rates of pathogens, which can alter the interface structure without compromising function (Harvey et al., Nature Reviews Microbiology, 2021).

Other names

Microbial surface protein-protein interfacesPathogen-host interfacesViral entry protein complexesBacterial adhesin interfacesMSCRAMMs

Inhibition of pathogen-host protein-protein interactions