Pilus chaperones represent a new type of protein-folding catalyst
Pilus chaperones represent a new type of protein-folding catalyst
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DOI：
10.1038/nature02891
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发表时间：
2004-09-16
期刊：
影响因子：
64.8
通讯作者：
Glockshuber, R
中科院分区：
文献类型：
--
作者：
Vetsch, M;Puorger, C;Glockshuber, R
尿路致病性大肠杆菌菌株的粘附1型皮利通过介导对宿主组织的粘附和潜在的侵入在感染过程中起着至关重要的作用。这些丝状的高度寡聚的蛋白质复合物通过“伴侣-引导”途径组装（1），其中单个菌毛亚基在细菌周质中折叠并与菌毛组装所必需的周质伴侣分子形成化学计量复合物（2-4）。分子伴侣随后将亚基递送至外膜中的组装平台（引导器），其介导亚基组装和易位至细胞表面（5-8）。在这里，我们表明，周质1型菌毛分子伴侣FimC结合非天然菌毛亚基和加速折叠的亚基FimG的100倍。此外，我们发现，FimC FimG复合物的形成定量和非常迅速的FimG折叠时，开始在FimC和组装能力亚基FimF的存在下，即使FimC-FimG复合物是化学稳定性低于FimF-FimG复合物。因此，FimC代表了一种以前未知类型的蛋白质折叠催化剂，同时作为一个动力学陷阱，防止自发的亚基组装在周质。
Adhesive type 1 pili from uropathogenic Escherichia coli strains have a crucial role during infection by mediating the attachment to and potentially the invasion of host tissue. These filamentous, highly oligomeric protein complexes are assembled by the 'chaperone-usher' pathway(1), in which the individual pilus subunits fold in the bacterial periplasm and form stoichiometric complexes with a periplasmic chaperone molecule that is essential for pilus assembly(2-4). The chaperone subsequently delivers the subunits to an assembly platform (usher) in the outer membrane, which mediates subunit assembly and translocation to the cell surface(5-8). Here we show that the periplasmic type 1 pilus chaperone FimC binds non-native pilus subunits and accelerates folding of the subunit FimG by 100-fold. Moreover, we find that the FimC FimG complex is formed quantitatively and very rapidly when folding of FimG is initiated in the presence of both FimC and the assembly-competent subunit FimF, even though the FimC-FimG complex is thermodynamically less stable than the FimF-FimG complex. FimC thus represents a previously unknown type of protein-folding catalyst, and simultaneously acts as a kinetic trap preventing spontaneous subunit assembly in the periplasm.