Most membrane enveloped viruses bud from infected cells by hijacking the host ESCRT machinery. The ESCRTs are recruited to bud sites by viral proteins that contain short proline-rich motifs (PRMs) known as late domains. The late domains probably evolved by co-opting host PRMs involved in the normal functions of ESCRTs in endosomal sorting and cytokinesis. The solution and crystal structures of PRMs bound to their interaction partners explain the conserved roles of Pro and other residues that predominate in these sequences. PRMs are often grouped together in much larger proline-rich regions (PRRs) of as many as 150 residues. The PRR of the ESCRT-associated protein ALIX autoregulates its conformation and activity. The robustness of different viral budding and host pathways to impairments in proline-based interactions varies considerably. The known biology of proline rich motif recognition in the ESCRT pathway seems, in principle, compatible with antiviral development, given our increasingly nuanced understanding of the relative weakness and robustness of the host and viral processes.
Keywords: protein structure, virus budding, ALG-2, endosome, cytokinesis, ALIX, TSG101, UEV domain, WW domain, CEP55