Fibres hinge on swapped domains

摘要

When proteins assemble themselves into fibres, there can be grave pathological consequences. Designing an otherwise soluble protein to make fibres provides a general mechanism for the construction process. DNA encodes RNA, which encodes protein — this central dogma', coined by Francis Crick in 1958, underpins modern molecular biology. Implicit in this formula is the tenet that a linear chain of amino acids contains the complete instructions to form a three-dimensional protein structure. Despite an astronomical number of possible configurations, a functional protein independently adopts the structure with the lowest free energy. These axioms are so universally observed that their violation holds particular fascination, A functional example of this is alpha-lytic protease, whose unfolded state is more stable than its native conformation. A pathological example of where the rules appear to be broken is when proteins aggregate into a form that is more stable than their functional precursors — a process found in a host of diseases, such as Alzheimer's, Hunting-ton's and prion diseases. In this issue, Sambashivan et al. (page 266) reconcile this apparent contradiction between dogma and observation.