signature=915e0df0ff1d0e5b75ad7a8ec65a1012,EC Accepts, published online ahead of print on 7 November...

摘要：

44 Introduction 45 Molecular chaperones assist the folding of other proteins during synthesis as well 46 as upon denaturation or misfolding. Prior results suggest that one type of molecular 47 chaperone assists folding of newly translated proteins, while a different set of molecular 48 chaperones help proteins fold after denaturation (1). The abundant essential chaperone 49 Hsp90 does not associate with nascent chains and does not appear to have a general role 50 in protein folding. Instead, Hsp90 is required for the folding and activation of a specific 51 subset of cellular proteins (2-4). Although it unlikely plays a general role in ribosomal 52 function, Hsp90 has been shown to be involved in polysome stability and to have 53 physical or genetic interactions with select proteins with ribosomal or pre-ribosomal 54 functions (5-8). 55 In Saccharomyces cerevisiae, Hsp90 is assisted by over ten co-chaperones that 56 target clients to Hsp90, directly or indirectly modulate Hsp90 ATPase activity, or have 57 other less defined functions (9). Many of the co-chaperones contain tetratricopeptide 58 repeat (TPR) domains and compete for binding to the conserved carboxy-terminal 59 MEEVD sequence of Hsp90. Three of the TPR-containing co-chaperones are Cpr6, Cpr7 60 and Cns1. Loss of CPR6 does not cause noticeable growth defects, loss of CPR7 results 61 in slow, temperature-sensitive growth and CNS1 is essential for viability (10-12). Cpr6 62 and Cpr7 share 38% amino acid identity yet exhibit different functions in vivo and in 63 vitro (13-16). In particular, overexpression of CPR7 rescues the temperature-sensitive 64 defect of cns1-G90D cells (17), while overexpression of CPR6 exacerbates the growth 65 defects (18). Further, overexpression of CNS1, but not CPR6, was able to rescue growth 66 defects of cpr7 cells (11-13). Yeast chaperones have been characterized as chaperones

展开