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In a homage to reductionism, Hongbin Li, Julio Fernandez (Columbia University, New York, NY), and colleagues show that the properties of individual domains of titin, a giant muscle protein, can explain the elasticity of intact muscle.
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5 Y, V5 o$ `; u) x0 LThe pulling in muscle is done by actin and myosin, but stretching is resisted by the elasticity of titin. Individual titin molecules of up to 3 MDa span over an entire half sarcomere〞the unit of contraction in muscle. But only one region of titin confers elasticity, and this region can be broken down into discrete domains.
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6 |( e' l. @- Y9 D' xFernandez and colleagues stretch various combinations of these domains by single molecule atomic force microscopy. They find that, under increasing force, proximal Ig domains undergo little passive stretching before giving way to a wholesale unfolding. The result is a sawtooth pattern of extension, with each peak representing the resistance of a single Ig domain.. S- J# L7 V; X S( \+ ? w0 N
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In contrast, the N2B domain can be stretched over a long distance with relatively little force. "N2B is behaving as a simple entropic spring," says Fernandez. This suggests that N2B does not have any significant fixed structural elements to resist stretching. "It's very hard to design a protein that will not attain some three-dimensional structure," said Fernandez. "It's clearly something that is not accidental and was meant to be this way."
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+ H1 D, S8 n5 s8 v2 `The extension of N2B and the similarly elastic PEVK domain explains most of the elastic behavior of titin. But at higher extensions some of the proximal Ig domains also unfold. "They serve as a gearbox," says Fernandez. Unfolding of an Ig domain creates a longer spring. This flexibility may allow muscle to operate at various levels of extension without the danger of breaking apart the sarcomere. Adding this effect to the calculations, and multiplying by the number of titin molecules present in a sarcomere, yields a curve that fits the behavior of intact muscle.
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Reference:% O$ Y. ^/ E9 r; x( u4 B8 i
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Li, H., et al. 2002. Nature. 418:998–1002.(Titin extends first via N2B unravelling ) |
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发表于 2009-3-6 00:20
发表于 2015-6-23 10:35
