| Structural highlights
Disease
BIP_HUMAN Autoantigen in rheumatoid arthritis.[1]
Function
BIP_HUMAN Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:G3I8R9][UniProtKB:P20029][2] [3] [4] [5] [6] [7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The 70-kDa heat shock proteins (Hsp70) are chaperones with central roles in processes that involve polypeptide remodeling events. Hsp70 proteins consist of two major functional domains: an N-terminal nucleotide binding domain (NBD) with ATPase activity, and a C-terminal substrate binding domain (SBD). We present the first crystal structures of four human Hsp70 isoforms, those of the NBDs of HSPA1L, HSPA2, HSPA5 and HSPA6. As previously with Hsp70 family members, all four proteins crystallized in a closed cleft conformation, although a slight cleft opening through rotation of subdomain IIB was observed for the HSPA5-ADP complex. The structures presented here support the view that the NBDs of human Hsp70 function by conserved mechanisms and contribute little to isoform specificity, which instead is brought about by the SBDs and by accessory proteins. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78.,Wisniewska M, Karlberg T, Lehtio L, Johansson I, Kotenyova T, Moche M, Schuler H PLoS One. 2010 Jan 11;5(1):e8625. PMID:20072699[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Corrigall VM, Bodman-Smith MD, Fife MS, Canas B, Myers LK, Wooley P, Soh C, Staines NA, Pappin DJ, Berlo SE, van Eden W, van Der Zee R, Lanchbury JS, Panayi GS. The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol. 2001 Feb 1;166(3):1492-8. PMID:11160188
- ↑ Ng DT, Watowich SS, Lamb RA. Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene. Mol Biol Cell. 1992 Feb;3(2):143-55. doi: 10.1091/mbc.3.2.143. PMID:1550958 doi:http://dx.doi.org/10.1091/mbc.3.2.143
- ↑ Oikawa D, Kimata Y, Kohno K, Iwawaki T. Activation of mammalian IRE1alpha upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins. Exp Cell Res. 2009 Sep 10;315(15):2496-504. doi: 10.1016/j.yexcr.2009.06.009., Epub 2009 Jun 16. PMID:19538957 doi:http://dx.doi.org/10.1016/j.yexcr.2009.06.009
- ↑ Dana RC, Welch WJ, Deftos LJ. Heat shock proteins bind calcitonin. Endocrinology. 1990 Jan;126(1):672-4. PMID:2294010
- ↑ Oka OB, Pringle MA, Schopp IM, Braakman I, Bulleid NJ. ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor. Mol Cell. 2013 Jun 27;50(6):793-804. doi: 10.1016/j.molcel.2013.05.014. Epub 2013, Jun 13. PMID:23769672 doi:http://dx.doi.org/10.1016/j.molcel.2013.05.014
- ↑ Evensen NA, Kuscu C, Nguyen HL, Zarrabi K, Dufour A, Kadam P, Hu YJ, Pulkoski-Gross A, Bahou WF, Zucker S, Cao J. Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration. J Natl Cancer Inst. 2013 Sep 18;105(18):1402-16. doi: 10.1093/jnci/djt224. Epub, 2013 Aug 29. PMID:23990668 doi:http://dx.doi.org/10.1093/jnci/djt224
- ↑ Cuevas EP, Eraso P, Mazon MJ, Santos V, Moreno-Bueno G, Cano A, Portillo F. LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway. Sci Rep. 2017 Mar 23;7:44988. doi: 10.1038/srep44988. PMID:28332555 doi:http://dx.doi.org/10.1038/srep44988
- ↑ Hassdenteufel S, Johnson N, Paton AW, Paton JC, High S, Zimmermann R. Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier. Cell Rep. 2018 May 1;23(5):1373-1386. doi: 10.1016/j.celrep.2018.03.122. PMID:29719251 doi:http://dx.doi.org/10.1016/j.celrep.2018.03.122
- ↑ Wisniewska M, Karlberg T, Lehtio L, Johansson I, Kotenyova T, Moche M, Schuler H. Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78. PLoS One. 2010 Jan 11;5(1):e8625. PMID:20072699 doi:10.1371/journal.pone.0008625
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