A bundling of viral fusion mechanisms.

M embrane fusion is a fundamental process in neurotransmission, vesicle trafficking, and infection by enveloped viruses. Mutational studies of class I viral fusion proteins have shown that simply pulling the two membranes together is not sufficient (1–3) to catalyze fusion in a physiological context: in these systems, a specific activity of the membrane-inserted peptides is required for full fusion. The precise mechanism of membrane activity has remained elusive. Although a number of hypotheses have been put forward (4), definitively establishing which combination of these contribute to fusion has been challenging. A combined structural and computational study published in PNAS (5) helps reinvigorate this debate. This article by Donald et al. (5) presents important conformational data on membrane-inserted fusion domains. Perhaps more significantly, it represents an emerging paradigm whereby computational studies can be used to help interpret mechanistic complexity in experimental data.