结构生物学sturcture biology explore-58.pdfVIP

231 Machinery of protein folding and unfolding Xiaodong Zhang*, Fabienne Beuron and Paul S Freemont† During the past two years, a large amount of biochemical, number of molecular machines have evolved to perform biophysical and low- to high-resolution structural data have both the unfolding (‘unfoldase’) and proteolysis activities. provided mechanistic insights into the machinery of protein Among these more specialised chaperone-assisted proteases folding and unfolding. It has emerged that dual functionality in are HslUV (heat shock locus UV), FtsH (a membrane- terms of folding and unfolding might exist for some systems. bound and ATP-dependent metalloprotease), ClpAP The majority of folding/unfolding machines adopt oligomeric (caseinolytic protease AP) and ClpXP. The disassembly of ring structures in a cooperative fashion and utilise the oligomeric protein complexes into their constituent folded conformational changes induced by ATP binding/hydrolysis for or partially folded parts requires a different class of machine. their specific functions. ‘Disassembler’ proteins include the ATPases NSF (N-ethylmaleimide-sensitive factor) and p97, both of Addresses which recycle essential components during vesicle Centre for Structural Biology, Department of Biological Sciences, membrane fusion [2]. Interestingly, many of the unfoldases Imperial College of Science, Technology and Medicine, Flowers and disassemblers belong to the large AAA+ (ATPase Building,