很多蛋白在高浓度时都形成纤维状结构，但蜘蛛网蛋白（有高度重复片段，侧面为非重复性末端区域）却有不同行为。它们在存放于高浓度时具有非常好的可溶性，但可根据需要转化成极为坚固的纤维。使这一点成为可能的分子机制尚不清楚，但本期Nature上两篇结构研究论文提供了新线索。

Askarieh等人发表了来自一种名为“Euprosthenops australis”的织网蜘蛛的一个拖丝蛋白“蜘蛛丝蛋白”的N-端区域的1.7X-射线晶体结构。该结构显示了这种高度保守的区域何以能够通过防止蜘蛛丝蛋白的过早积累、以及通过在pH值降低时沿蜘蛛丝伸出管触发聚合反应来调控蜘蛛丝的组装。

Hagn等人确定了来自常见园蛛科蜘蛛“Araneus diadematus”的拖丝蛋白“丝心蛋白-3”的C-端NR区域的溶液结构。他们观察到了该蛋白的存储和组装形式之间由化学或机械刺激激发的一个构形切换。

原文出处：
 
Nature doi:10.1038/nature08962

Self-assembly of spider silk proteins is controlled by a pH-sensitive relay
Glareh Askarieh1,2,5, My Hedhammar3,5, Kerstin Nordling3, Alejandra Saenz4, Cristina Casals4, Anna Rising3, Jan Johansson3 & Stefan D. Knight2

1Department of Chemistry, Oslo University, 1033 Blindern, 0315 Oslo, Norway
2Department of Molecular Biology, Uppsala BioCenter, SLU, Biomedical Centre, P.O. Box 590, SE-751 24 Uppsala, Sweden
3Department of Anatomy, Physiology and Biochemistry, SLU, Biomedical Centre, P.O. Box 575, SE-751 23 Uppsala, Sweden
4Department of Biochemistry and Molecular Biology I & CIBER Enfermedades Respiratorias, Complutense University of Madrid, 28040-Madrid, Spain
5These authors contributed equally to this work

Nature’s high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains1, 2. Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide strength and elasticity3, 4. How spiders manage to avoid premature spidroin aggregation before self-assembly is not yet established. A pH drop to 6.3 along the spider’s spinning apparatus, altered salt composition and shear forces are believed to trigger the conversion to solid silk, but no molecular details are known. Miniature spidroins consisting of a few repetitive spidroin segments capped by the carboxy-terminal domain form metre-long silk-like fibres irrespective of pH5. We discovered that incorporation of the amino-terminal domain of major ampullate spidroin 1 from the dragline of the nursery web spider Euprosthenops australis (NT) into mini-spidroins enables immediate, charge-dependent self-assembly at pH values around 6.3, but delays aggregation above pH?7. The X-ray structure of NT, determined to 1.7?? resolution, shows a homodimer of dipolar, antiparallel five-helix bundle subunits that lack homologues. The overall dimeric structure and observed charge distribution of NT is expected to be conserved through spider evolution and in all types of spidroins. Our results indicate a relay-like mechanism through which the N-terminal domain regulates spidroin assembly by inhibiting precocious aggregation during storage, and accelerating and directing self-assembly as the pH is lowered along the spider’s silk extrusion duct.