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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eukaryotic cells contain multiple Hsp70 proteins and DnaJ homologues. The partnership between a given Hsp70 and its interacting DnaJ could, in principle, be determined by their cellular colocalization or by specific protein-protein interactions. The yeast SCJ1 gene encodes one of several homologues of the bacterial chaperone DnaJ. We show that Scj1p is located in the lumen of the endoplasmic reticulum (ER), where it can function with Kar2p (the ER-lumenal BiP/Hsp70 of yeast). The region common to all DnaJ homologues (termed the J domain) from Scj1p can be swapped for a similar region in Sec63p, which is known to interact with Kar2p in the ER lumen, to form a functional transmembrane protein component of the secretory machinery. Thus, Kar2p can interact with two different DnaJ proteins. On the other hand, J domains from two other non-ER DnaJs, Sis1p and Mdj1p, do not function when swapped into Sec63p. However, only three amino acid changes in the Sis1p J domain render the Sec63 fusion protein fully functional in the ER lumen. These results indicate that the choice of an Hsp70 partner by a given DnaJ homologue is specified by the J domain.
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PMID:A yeast DnaJ homologue, Scj1p, can function in the endoplasmic reticulum with BiP/Kar2p via a conserved domain that specifies interactions with Hsp70s. 774 69

BiP (Kar2 in yeast) is an essential Hsp70 chaperone and master regulator of endoplasmic reticulum (ER) function. BiP's activity is regulated by its intrinsic ATPase activity that can be stimulated by two different nucleotide exchange factors, Sil1 and Lhs1. Both Sil1 and Lhs1 are glycoproteins, but how N-glycosylation regulates their function is not known. Here, we show that N-glycosylation of Sil1, but not of Lhs1, is diminished upon reductive stress. N-glycosylation of Sil1 is predominantly Ost3-dependent and requires a functional Ost3 CxxC thioredoxin motif. N-glycosylation of Lhs1 is largely Ost3-independent and independent of the CxxC motif. Unglycosylated Sil1 is not only functional but is more effective at rescuing loss of Lhs1 activity than N-glycosylated Sil1. Furthermore, substitution of the redox active cysteine pair C52 and C57 in the N terminus of Sil1 results in the Doa10-dependent ERAD of this mutant protein. We propose that reductive stress in the ER inhibits the Ost3-dependent N-glycosylation of Sil1, which regulates specific BiP functions appropriate to the needs of the ER under reductive stress.
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PMID:Diminished Ost3-dependent N-glycosylation of the BiP nucleotide exchange factor Sil1 is an adaptive response to reductive ER stress. 2910 65

BiP is the endoplasmic member of the Hsp70 family. BiP is regulated by several co-chaperones including the nucleotide-exchange factor (NEF) Bap (Sil1 in yeast). Bap is a two-domain protein. The interaction of the Bap C-terminal domain with the BiP ATPase domain is sufficient for its weak NEF activity. However, stimulation of the BiP ATPase activity requires full-length Bap, suggesting a complex interplay of these two factors. Here, single-molecule FRET experiments with mammalian proteins reveal that Bap affects the conformation of both BiP domains, including the lid subdomain, which is important for substrate binding. The largely unstructured Bap N-terminal domain promotes the substrate release from BiP. Thus, Bap is a conformational regulator affecting both nucleotide and substrate interactions. The preferential interaction with BiP in its ADP state places Bap at a late stage of the chaperone cycle, in which it coordinates release of substrate and ADP, thereby resetting BiP for ATP and substrate binding.
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PMID:Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate. 2932 81