PMC:2195774 / 16216-17991 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2195774","sourcedb":"PMC","sourceid":"2195774","source_url":"http://www.ncbi.nlm.nih.gov/pmc/2195774","text":"The COOH Terminus of Sis1 Can Substitute for the COOH Terminus of Ydj1 In Vivo, but Only in Cis\nThe results presented above indicate that substrate binding is critical for Hsp40 function. In the current model of interaction between substrates, Hsp40 and Hsp70, substrate first bind the COOH terminus of Hsp40 and then are targeted to Hsp70 via interaction of the J domain with the ATPase domain of Hsp70 (Langer et al. 1992; Liberek et al. 1995; Laufen et al. 1999). The J domain of both Ydj1 and Sis1 have been shown to be important in vivo, as a single amino acid change in either J domain has severe effects on function. In a ydj1 disruption strain, an F47L alteration of Ydj1 causes both severe growth defects and defects in the maturation of Hsp90 substrates (Johnson and Craig 2000). The H34Q mutation of Sis1 disrupts the HPD motif in the J domain and causes a null phenotype in an sis1 disruption strain (Yan and Craig 1999).\nWe conducted in vivo tests to determine whether a functional J domain and COOH-terminal substrate-binding domain must be part of the same protein (Fig. 4). Growth of an sis1 ydj1 strain expressing sis1-121 and ydj1-134 could not be rescued by either H34Q Sis1 or F47L Ydj1. Nor did the COOH-terminal fragment of Sis1 (a.a. 170–352) expressed in trans with J plus G/F allow viability. These results indicate that the COOH terminus of Sis1 must be present in the context of a wild-type J domain to function, indicating that close cooperation between the two domains is essential for function in vivo. However, in support of the idea that the COOH-terminal regions can substitute for one another, a fusion protein (YYS-262) that joins the G/M region and domain I of Sis1 to the J plus G/F of Ydj1 (Yan and Craig 1999) allows viability (Fig. 4).","divisions":[{"label":"Title","span":{"begin":0,"end":95}}],"tracks":[]}