Flat clathrin lattices or 'plaques' are commonly believed to be the precursors to clathrin-coated buds and vesicles. The sequence of steps carrying the flat hexagonal lattice into a highly curved polyhedral cage with exactly 12 pentagons remains elusive, however, and the large numbers of disrupted interclathrin connections in previously proposed conversion pathways make these scenarios rather unlikely. The recent notion that clathrin can make controlled small conformational transitions opens new avenues. Simulations with a self-assembling clathrin model suggest that localized conformational changes in a plaque can create sufficiently strong stresses for a dome-like fragment to break apart. The released fragment, which is strongly curved but still hexagonal, may subsequently grow into a cage by recruiting free triskelia from the cytoplasm, thus building all 12 pentagonal faces without recourse to complex topological changes. The critical assembly concentration in a slightly acidic in vitro solution is used to estimate the binding energy of a cage at 25-40 k(B) T/clathrin.
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