Key points are not available for this paper at this time.
Specification of Hsp70 action in cellular protein metabolism may occur through the formation of specialized Hsp70:Hsp40 pairs. To test this model, we compared the ability of purified Sis1 and Ydj1 to regulate the ATPase and protein-folding activity of Hsp70 Ssa1 and Ssb1/2 proteins. Ydj1 and Sis1 could both functionally interact with Ssa1, but not the Ssb1/2 proteins, to refold luciferase. Interestingly, Ydj1:Ssa1 could promote up to four times more luciferase folding than Sis1:Ssa1. This functional difference was explored and could not be accounted for by differences in the ability of Sis1 and Ydj1 to regulate Ssa1 ATPase activity. Instead, differences in the chaperone function of Ydj1 and Sis1 were observed. Ydj1 was dramatically more effective than Sis1 at suppressing the thermally induced aggregation of luciferase. Paradoxically, Sis1 and Ydj1 could bind similar quantities of chemically denatured luciferase. The polypeptide binding domain of Sis1 was found to lie between residues 171–352 and correspond to its conserved carboxyl terminus. The conserved carboxyl terminus of Ydj1 is also known to participate in the binding of nonnative polypeptides. Thus, Ydj1 appears more efficient at assisting Ssa1 in folding luciferase because its contains a zinc finger-like region that is absent from Sis1. Ydj1 and Sis1 are structurally and functionally distinct Hsp40 proteins that can specify Ssa1 action by generating Hsp70:Hsp40 pairs that exhibit different chaperone activities. Specification of Hsp70 action in cellular protein metabolism may occur through the formation of specialized Hsp70:Hsp40 pairs. To test this model, we compared the ability of purified Sis1 and Ydj1 to regulate the ATPase and protein-folding activity of Hsp70 Ssa1 and Ssb1/2 proteins. Ydj1 and Sis1 could both functionally interact with Ssa1, but not the Ssb1/2 proteins, to refold luciferase. Interestingly, Ydj1:Ssa1 could promote up to four times more luciferase folding than Sis1:Ssa1. This functional difference was explored and could not be accounted for by differences in the ability of Sis1 and Ydj1 to regulate Ssa1 ATPase activity. Instead, differences in the chaperone function of Ydj1 and Sis1 were observed. Ydj1 was dramatically more effective than Sis1 at suppressing the thermally induced aggregation of luciferase. Paradoxically, Sis1 and Ydj1 could bind similar quantities of chemically denatured luciferase. The polypeptide binding domain of Sis1 was found to lie between residues 171–352 and correspond to its conserved carboxyl terminus. The conserved carboxyl terminus of Ydj1 is also known to participate in the binding of nonnative polypeptides. Thus, Ydj1 appears more efficient at assisting Ssa1 in folding luciferase because its contains a zinc finger-like region that is absent from Sis1. Ydj1 and Sis1 are structurally and functionally distinct Hsp40 proteins that can specify Ssa1 action by generating Hsp70:Hsp40 pairs that exhibit different chaperone activities. Hsp70 proteins play an essential physiological role by protecting cells from stress, promoting protein folding, driving protein translocation across membranes, mediating the assembly and disassembly of macromolecular complexes, and facilitating protein degradation (1Georgopoulos C. Welch W.J. Annu. Rev. Cell Biol. 1993; 9: 601-634Crossref PubMed Scopus (1004) Google Scholar, 2Hartl F.U. Nature. 1996; 381: 571-579Crossref PubMed Scopus (3137) Google Scholar, 3Neupert W. Hartl F.U. Craig E.A. Pfanner N. Cell. 1990; 63: 447-450Abstract Full Text PDF PubMed Scopus (182) Google Scholar, 4Schatz G. Dobberstein B. Science. 1996; 271: 1519-1526Crossref PubMed Scopus (923) Google Scholar). Hsp70 facilitates these different types of biochemical reactions via an ATP-dependent mechanism that involves the binding and release of short segments of polypeptides that exist in extended conformations (5Bukau B. Horwich A.L. Cell. 1998; 92: 351-366Abstract Full Text Full Text PDF PubMed Scopus (2443) Google Scholar). Since Hsp70 has a very broad substrate specificity, a major issue concerning the mechanism of its action is what determines the cellular reactions it catalyzes. Cells contain multiple Hsp70 family members that share around 60% sequence identity with the largest degree of variation being observed in their polypeptide binding domains (5Bukau B. Horwich A.L. Cell. 1998; 92: 351-366Abstract Full Text Full Text PDF PubMed Scopus (2443) Google Scholar). Thus, it is plausible that structural differences in the polypeptide binding grooves of Hsp70 proteins help determine which reactions they catalyze. Such a mechanism is supported by the observation that Hsp70 proteins that are localized in the cytosol and lumen of the endoplasmic reticulum are not interchangeable (6Brodsky J.L. Hamamoto S. Feldheim D. Schekman R. J. Cell Biol. 1993; 120: 95-102Crossref PubMed Scopus (130) Google Scholar). In addition, the yeast cytosol contains two different forms of Hsp70, Ssa1–4 and Ssb1–2 proteins, which have distinct functions and exhibit a high degree of sequence dissimilarity in regions predicated to be involved in polypeptide binding (7Slater M.R. Craig E.A. Nucleic Acids Res. 1989; 17: 4891Crossref PubMed Scopus (18) Google Scholar, 8Slater M.R. Craig E.A. Nucleic Acids Res. 1989; 17: 805-806Crossref PubMed Scopus (42) Google Scholar, 9Craig E.A. Gambill B.D. Nelson R.J. Microbiol. Rev. 1993; 57: 402-414Crossref PubMed Google Scholar). However, swapping the polypeptide binding domains of Ssa and Ssb proteins does not alter the specificity of their action (10James P. Pfund C. Craig E.A. Science. 1997; 275: 387-389Crossref PubMed Scopus (185) Google Scholar). Therefore, factors other than the substrate specificity of Hsp70 must influence the fidelity of the biochemical reactions it catalyzes. Likely candidates for these specificity factors are co-chaperones that have been identified as regulators of the Hsp70 action (11Liberek K. Marszalek J. Ang D. Georgopoulos C. Zylicz M. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 2874-2878Crossref PubMed Scopus (694) Google Scholar, 12Georgopoulos C. Trends Biochem. Sci. 1992; 17: 295-299Abstract Full Text PDF PubMed Scopus (201) Google Scholar, 13Cyr D.M. Lu X. Douglas M.G. J. Biol. Chem. 1992; 267: 20927-20931Abstract Full Text PDF PubMed Google Scholar, 14Hohfeld J. Minami Y. Hartl F.U. Cell. 1995; 83: 589-598Abstract Full Text PDF PubMed Scopus (381) Google Scholar, 15Takayama S. Bimston D.N. Matsuzawa S. Freeman B.C. Aime-Sempe C. Xie Z. Morimoto R.I. Reed J.C. EMBO J. 1997; 16: 4887-4896Crossref PubMed Scopus (439) Google Scholar, 16Johnson B.D. Schumacher R.J. Ross E.D. Toft D.O. J. Biol. Chem. 1998; 273: 3679-3686Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar). Hsp40 (DnaJ-related proteins) co-chaperones function as molecular chaperones and regulators of Hsp70 ATPase activity (17Cyr D.M. Langer T. Douglas M.G. Trends Biochem. Sci. 1994; 19: 176-181Abstract Full Text PDF PubMed Scopus (403) Google Scholar, 18Cyr D.M. Gething M.-J. Guidebook to Molecular Chaperones and Protein Folding Factors. Oxford University Press, Oxford1997: 89-95Google Scholar). Two features of the Hsp40 family would enable them to direct Hsp70 to catalyze specific types of reactions in protein metabolism. First, multiple Hsp40 proteins are present in subcellular compartments, and they are often concentrated to different locations, which enables Hsp70 to catalyze localized reactions in protein metabolism. Second, Hsp40 family members have different domain structures and are therefore not functional equivalents (19Caplan A.J. Cyr D.M. Douglas M.G. Cell. 1992; 71: 1143-1155Abstract Full Text PDF PubMed Scopus (219) Google Scholar, 20Caplan A.J. Cyr D.M. Douglas M.G. Mol. Biol. Cell. 1993; 4: 555-563Crossref PubMed Scopus (196) Google Scholar). Hsp40 family members contain different combinations of four conserved domains initially identified in Escherichia coli DnaJ (21Georgopoulos C.P. Lundquist-Heil A. Yochem J. Feiss M. Mol. Gen. Genet. 1980; 178: 583-588Crossref PubMed Scopus (53) Google Scholar), which include the J-domain, G/F-rich region, zinc finger-like domain, and conserved carboxyl terminus. The J-domain corresponds to the amino-terminal 70-amino acid residues of DnaJ and is found in all Hsp40 proteins and is responsible for regulation of the ATP hydrolytic cycle of Hsp70 (22Wall D. Zylicz M. Georgopoulos C. J. Biol. Chem. 1994; 269: 5446-5451Abstract Full Text PDF PubMed Google Scholar, 23Jordan R. McMacken R. J. Biol. Chem. 1995; 270: 4563-4569Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). The G/F-rich region is present in approximately 50% of Hsp40 family members, appears to function as a spacer between the J-domain and other regions of Hsp40 proteins, and may directly interact with Hsp70 (23Jordan R. McMacken R. J. Biol. Chem. 1995; 270: 4563-4569Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar,25Wall D. Zylicz M. Georgopoulos C. J. Biol. Chem. 1995; 270: 2139-2144Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar). The zinc finger-like region and the conserved carboxyl terminus are also present in different combinations in nearly 50% of Hsp40 family members and are both involved in interactions with nonnative polypeptides (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar, 26Szabo A. Korszun R. Hartl F.U. Flanagan J. EMBO J. 1996; 15: 408-417Crossref PubMed Scopus (276) Google Scholar, 27Banecki B. Liberek K. Wall D. Wawrzynow A. Georgopoulos C. Bertoli E. Tanfani F. Zylicz M. J. Biol. Chem. 1996; 271: 14840-14848Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar). A subfamily of Hsp40 proteins contains only the J-domain and other specialized domains that allow them to bind specific substrates or localize them to discrete locations within the cell (18Cyr D.M. Gething M.-J. Guidebook to Molecular Chaperones and Protein Folding Factors. Oxford University Press, Oxford1997: 89-95Google Scholar). Thus, it is possible that a single form of Hsp70 can interact with different subtypes of Hsp40 proteins to generate functionally distinct Hsp70:Hsp40 chaperone machines. The specific recognition and pairing of Hsp40 proteins with different subfamily members may also provide a mechanism to dictate Hsp70 action. For example, the chaperone action of the Ssa, but not the Ssb proteins, can be regulated by the cytosolic Hsp40 protein Ydj1 (28Cyr D.M. FEBS Lett. 1995; 359: 129-132Crossref PubMed Scopus (115) Google Scholar, 29Cyr D.M. Douglas M.G. J. Biol. Chem. 1994; 269: 9798-9804Abstract Full Text PDF PubMed Google Scholar). There is also genetic evidence to support speculation that the Ssb proteins are specifically regulated by a different cytosolic Hsp40 protein termed Sis1 with Ssa:Ydj1 and Ssb:Sis1, representing independent Hsp70 chaperone systems (30Ohba M. FEBS Lett. 1997; 409: 307-311Crossref PubMed Scopus (38) Google Scholar). However, the ability of Sis1 to regulate the action of the Ssb proteins has not been directly demonstrated. In addition, differences in results obtained from genetic studies may reflect the fact that Ydj1 contains all four of the conserved domains of DnaJ, whereas Sis1 lacks the zinc finger-like region. To investigate how Hsp40 proteins specify cellular actions of Hsp70, we examined the ability of purified Sis1 and Ydj1 to regulate the protein folding activity of Ssa1 and Ssb1/2. that Sis1 and Ydj1 both the ability Ssa1 to luciferase but not interact with Ssb1/2. Interestingly, the was found to be up to four times more efficient than the in folding luciferase. This in Sis1 and Ydj1 function to from a difference in their ability to function as molecular Thus, Ssa1 specifically with at two Hsp40 proteins, and the chaperone activity of its the action of the different Hsp70:Hsp40 pairs Hsp70 Ssa1 and a of Ssb1/2 were purified as D.M. Lu X. Douglas M.G. J. Biol. Chem. 1992; 267: 20927-20931Abstract Full Text PDF PubMed Google Scholar, 29Cyr D.M. Douglas M.G. J. Biol. Chem. 1994; 269: 9798-9804Abstract Full Text PDF PubMed Google Scholar). The and proteins are approximately and as a D.M. Douglas M.G. J. Biol. Chem. 1994; 269: 9798-9804Abstract Full Text PDF PubMed Google and are therefore to as Ssb1/2 in the Ssa1 contains than a with Ssb proteins, and the Ssb1/2 contains a with D.M. Douglas M.G. J. Biol. Chem. 1994; 269: 9798-9804Abstract Full Text PDF PubMed Google Scholar). Ydj1 was with residues at its terminus and purified by (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). To a was its terminus by The was the and of was in via of with and at for Cell from of and were in of and Cell were by and cell were at a of with The was with of and of with was with an and were were and concentrated to to in and at purified in this was than The of a to the terminus of Ydj1 or to of Sis1 does not alter the ability of the forms of these proteins to observed in that or A. J. Cell Biol. 1991; PubMed Scopus Google not In addition, and similar to the forms of these proteins in for and chaperone function 24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google not Ssa1 or Ssb1/2 was in a and ATP for at were and were for formation by D.M. Lu X. Douglas M.G. J. Biol. Chem. 1992; 267: 20927-20931Abstract Full Text PDF PubMed Google Scholar). formation was and for of ATP The of Hsp70 ATPase activity were for at these D.M. Lu X. Douglas M.G. J. Biol. Chem. 1992; 267: 20927-20931Abstract Full Text PDF PubMed Google Scholar). A of luciferase in a and was the that and Ssa1 as The was at for by to a that its to of luciferase aggregation were by in at Y. J. K. Hartl F.U. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). of chemically denatured luciferase by Hsp70 and Hsp40 was as (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). luciferase was and The was to for at and a was and with of that was with the chaperone proteins and at of were from the folding reactions at the times and with of luciferase activity was with a The of luciferase activity observed Ydj1 and Ssa1 were present in was to around of the activity by the protein from was chemically denatured as and was and the of Hsp40 proteins and for at The was with of a 50% of that been for in the to were extended for an The proteins with the were by of the at for at in a The was and the was with a and to that was between and denatured luciferase were from the by the of of a and by at for an were in a as and the of the were concentrated by with were and were with The of luciferase to Sis1 and Ydj1 was with a Sis1 was to (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). and molecular of the of Sis1 by this was also as (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). of formation between of Sis1 and luciferase was as To functional interactions between Hsp40 and Hsp70 proteins in the yeast we compared the ability of purified Sis1 and Ydj1 to the luciferase folding activity of Ssa1 and Ssb1/2 luciferase was denatured with and folding that different and combinations of chaperone proteins. the of luciferase were Ssa1, or Ydj1 were only a of and pairs of Ssb1/2 and Sis1 or Ydj1 were we observed in luciferase activity. In Sis1 and Ydj1 were both of the ability of Ssa1 to refold luciferase. folding activity for both the and pairs was observed at a and activity was observed at a Interestingly, the was approximately more effective than the in folding luciferase. Thus, Sis1 and Ydj1 to interact with Ssa1 of Ssb1/2 to promote protein metabolism in the we differences in and activity are also observed these chaperone pairs are with thermally denatured luciferase of the chemically form of this the Ssb1/2 proteins were not in the folding of chemically denatured they were not in this luciferase was by at in the or of chaperone proteins, and its was to and The could luciferase from aggregation and promote its to a that was approximately than that observed in the of these The chaperone luciferase than of Hsp70 by the of and of in of the folding action by the and pairs. Thus, both Sis1 and Ydj1 the ATP-dependent action of Ssa1 in folding denatured but in this the and pairs are not functionally and chaperone pairs exhibit differences in their ability to Sis1 and Ydj1 the ability of Ssb1/2 to refold Hsp40 proteins exhibit differences in their ability to regulate the ATP hydrolytic cycle of In of this both Sis1 and Ydj1 were observed to the ATPase activity of Ssa1 by to but ATP by Ssb1/2 Ydj1 the ATPase of Ssa1 and Ssb1/2 by and Sis1 the ATPase of Ssa1 and Ssb1/2 by and The differences in the ability of Ydj1 and Sis1 to the ATPase activity of Ssa1 were not In addition, the of Ssb1/2 ATPase by Sis1 and Ydj1 could be accounted for by of this protein with Ssa protein D.M. Douglas M.G. J. Biol. Chem. 1994; 269: 9798-9804Abstract Full Text PDF PubMed Google Scholar). The of Sis1 and Ydj1 to the ATPase activity of Ssb1/2 protein appears to these co-chaperones not this Hsp70 in folding luciferase. However, a mechanism to regulation of ATP is to for the in the protein folding of and in the chaperone function of Sis1 and Ydj1 may for their ability to regulate Ssa1 action in luciferase To investigate this the ability of Sis1 and Ydj1 to luciferase in a was examined Ssa1, or Sis1 were the of luciferase at the for these chaperones was to a of the that was at only Ssa1 was present the of luciferase activity was observed Ydj1 was to the luciferase activity could be Ydj1 was the and Ssa1 was in the In in luciferase activity was observed Sis1 was the and Ssa1 was of these results is that Ydj1 is more efficient than Sis1 at suppressing thermally induced aggregation of luciferase and therefore is more effective at luciferase in This was directly by the ability of Sis1 and Ydj1 to the aggregation of thermally denatured luciferase at luciferase with a of Sis1 at up to influence luciferase aggregation In Ydj1 was to this in a with than being observed at Sis1 not function as a chaperone it was of with Ssa1 to luciferase In the and pairs were both of to luciferase aggregation by and Thus, Sis1 and Ssa1 can function to protein aggregation in a that is similar to the activity of However, Sis1 is efficient than Ydj1 at independent of Ssa1 to luciferase Ydj1 and Sis1 exhibit differences in their chaperone Sis1 and Ydj1 may exhibit ability to bind and this be these proteins are not as molecular To directly this we compared the ability of and to form with chemically denatured luciferase Sis1 and Ydj1 were at with luciferase Sis1 and Ydj1 both luciferase but not to interact with forms of this protein and of denatured luciferase by Sis1 and Ydj1 was also the of the chaperone proteins in the binding Sis1 and Ydj1 could be in a with approximately of the luciferase and Hsp40 in formation was observed results that at Sis1 and Ydj1 bind all of the denatured luciferase present in However, these to because formation is an (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar, Y. J. K. Hartl F.U. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, T. Lu C. Flanagan J. Hartl F.U. Nature. 1992; PubMed Scopus Google Scholar). Sis1 can and bind nonnative polypeptides and therefore can be as a molecular However, these not Sis1 is efficient than Ydj1 at Ssa1 to luciferase. that how Hsp40 proteins bind polypeptides is that a of Ydj1 that contains a of the zinc finger-like region and the conserved carboxyl terminus chaperone function similar to Ydj1 (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). However, Sis1 lacks the zinc finger-like region, it is that the conserved carboxyl terminus of Hsp40 proteins is for substrate To test this and the region of Hsp40 proteins that contains their polypeptide binding the domain of Sis1 was by with Sis1 two major a and a of DnaJ and Ydj1 a that corresponds to the J-domain (23Jordan R. McMacken R. J. Biol. Chem. 1995; 270: 4563-4569Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). Therefore, we that the of Sis1 was of similar and not investigate its identity or function The Sis1 was by amino-terminal acid and and was found to have a molecular of and acid residues at its terminus. The of Sis1 therefore corresponds to residues 171–352 A. J. Cell Biol. 1991; PubMed Scopus Google Scholar). Sis1 the region in Sis1 that corresponds to the conserved carboxyl terminus of Hsp40 proteins. Therefore, we to its ability to bind polypeptides with Sis1. However, to Sis1 in luciferase binding we to it with a its carboxyl terminus. was and for its ability to regulate Hsp70 ATPase activity and with Ssa1 to protein from these that the activity as and Sis1 not was with to determine a similar to Sis1 could be to be a that with a than Sis1 that this a molecular of which was nearly to the molecular of for Sis1 The from therefore corresponds to Sis1 with residues to its carboxyl terminus. the ability of Sis1 to bind denatured luciferase was compared with and Sis1 could bind quantities of luciferase that were similar to and of luciferase by and Sis1 was the of luciferase in and both proteins to have for proteins in the The polypeptide binding domain of Sis1 corresponds to a region within its conserved carboxyl terminus. Therefore, similar regions within Ydj1 and Sis1 are in polypeptide also for the that the conserved carboxyl terminus of an Hsp40 protein can function to and bind nonnative polypeptides. that the Ssa proteins, but not the interact with at two different subtypes of Hsp40 to form Hsp70:Hsp40 chaperone that luciferase with different The mechanism by which Sis1 and Ydj1 Ssa1 action in luciferase folding is to differences in their chaperone functions and not regulation of ATPase activity. Ydj1 and Sis1 are functionally distinct Hsp40 proteins that specify Ssa1 action by generating Hsp70:Hsp40 pairs that have different chaperone activities. The results the biochemical of Sis1. that Sis1 can regulate Ssa1 ATPase activity and function as a molecular However, Sis1 and Ydj1 are not Sis1 is efficient than Ydj1 at thermally denatured luciferase in and is therefore efficient at Paradoxically, Sis1 and Ydj1 bind chemically denatured luciferase in a similar Sis1 lacks the zinc finger-like domain that is present in this structural dissimilarity may for differences in the of these of the zinc finger-like region of Ydj1 its ability to Hsp70 in luciferase but does not its ability to bind denatured protein (24Lu Z. Cyr D.M. J. Biol. Chem. 1998; 273: 5970-5978Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar). the zinc finger-like region the protein folding activity of Ydj1 is identified the conserved carboxyl terminus as the polypeptide binding domain of Sis1 and have this domain to participate in protein folding by Therefore, it that other Hsp40 family members that contain the conserved carboxyl terminus but the zinc finger-like region, as Y. J. K. Hartl F.U. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, B.C. Morimoto R.I. EMBO J. 1996; 15: PubMed Scopus Google Scholar, K. M. B. M. J. Cell Biol. 1997; PubMed Scopus Google and C. M. T. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar), can also function as molecular In Hsp40 proteins that contain the zinc finger-like region to the conserved carboxyl terminus. the zinc finger-like region of DnaJ that it can directly interact with proteins A. Korszun R. Hartl F.U. Flanagan J. EMBO J. 1996; 15: 408-417Crossref PubMed Scopus (276) Google and influence interactions between DnaJ and E. coli Hsp70 B. Liberek K. Wall D. Wawrzynow A. Georgopoulos C. Bertoli E. Tanfani F. Zylicz M. J. Biol. Chem. 1996; 271: 14840-14848Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar). Therefore, can that the zinc finger-like region directly the conserved carboxyl terminus in substrate binding or a structural role in the polypeptide binding of that the for polypeptide binding and release by Ydj1 and Sis1 are to and chaperone pairs are not functionally The observed differences in the biochemical activity of purified Ydj1 and Sis1 are with genetic studies that that these co-chaperones not play in cell A.J. Douglas M.G. J. Cell Biol. 1991; PubMed Scopus Google Scholar). is an essential whereas is essential only for at A. J. Cell Biol. 1991; PubMed Scopus Google Scholar, A.J. Douglas M.G. J. Cell Biol. 1991; PubMed Scopus Google Scholar). of Sis1 can the of but Ydj1 the of A. J. Cell Biol. 1991; PubMed Scopus Google Scholar, A.J. Douglas M.G. J. Cell Biol. 1991; PubMed Scopus Google Scholar). Ydj1 appears to Sis1 as a it is that the of However, Ydj1 is a protein in (19Caplan A.J. Cyr D.M. Douglas M.G. Cell. 1992; 71: 1143-1155Abstract Full Text PDF PubMed Scopus (219) Google A.J. J. Douglas M.G. J. Biol. Chem. 1992; 267: Full Text PDF PubMed Google Scholar), and this may its ability to for Sis1 in the of essential cellular and pairs have been to independent chaperone systems (30Ohba M. FEBS Lett. 1997; 409: 307-311Crossref PubMed Scopus (38) Google Scholar). Sis1 was of Ssb ATPase and luciferase folding not support the However, the genetic evidence that that Sis1 and Ssb in protein independent of Ssa or Ydj1 not be (30Ohba M. FEBS Lett. 1997; 409: 307-311Crossref PubMed Scopus (38) Google Scholar). is possible that with purified of the Ssb proteins to functionally interact with Sis1 of the mechanism for Ssb function is to this of the University of Protein was responsible for of the of the Protein was responsible for the Sis1 was the of the of which is in the
Lü et al. (Thu,) studied this question.