The primary substrate binding site in the b' domain of ERp57 is adapted for endoplasmic reticulum lectin association - PubMed (original) (raw)
. 2004 Apr 30;279(18):18861-9.
doi: 10.1074/jbc.M400575200. Epub 2004 Feb 10.
Affiliations
- PMID: 14871899
- DOI: 10.1074/jbc.M400575200
Free article
The primary substrate binding site in the b' domain of ERp57 is adapted for endoplasmic reticulum lectin association
Sarah J Russell et al. J Biol Chem. 2004.
Free article
Abstract
ERp57 is a member of the protein disulfide isomerase (PDI) family that is located in the endoplasmic reticulum (ER) and characterized by its specificity for glycoproteins. Substrate selection by ERp57 is dependent upon its formation of discrete complexes with two ER resident lectins, soluble calreticulin and membrane-bound calnexin. It is these two lectins that directly associate with glycoproteins bearing correctly trimmed oligosaccharide side chains. Thus, ERp57 is presented with a preselected set of substrates upon which it can act, and the specific binding of calreticulin and calnexin to ERp57 is pivotal to the functions of the resulting complexes. To gain further insights into the formation of these ERp57-ER lectin complexes, we have investigated the regions of ERp57 that are specifically required for its binding to calreticulin. Using a quantitative pull-down assay to investigate the binding of ERp57/PDI chimeras to calreticulin, we define the b and b' domains of ERp57 as the minimal elements that are sufficient for complex formation. This analysis further identifies a novel role for the distinctive C-terminal extension of ERp57 in reconstituting complex formation to wild type levels. Using our understanding of substrate binding to the b' domain of PDI as a paradigm, we show that alterations to specific residues in the b' domain of ERp57 dramatically reduce or completely abolish its binding to calreticulin. On the basis of these data, we propose a model where the region of ERp57 equivalent to the primary substrate binding site of archetypal PDI is occupied by calreticulin and suggest that the ER lectins act as adaptor molecules that define the substrate specificity of ERp57.
Similar articles
- ERp57 functions as a subunit of specific complexes formed with the ER lectins calreticulin and calnexin.
Oliver JD, Roderick HL, Llewellyn DH, High S. Oliver JD, et al. Mol Biol Cell. 1999 Aug;10(8):2573-82. doi: 10.1091/mbc.10.8.2573. Mol Biol Cell. 1999. PMID: 10436013 Free PMC article. - Identification and characterization of structural domains of human ERp57: association with calreticulin requires several domains.
Silvennoinen L, Myllyharju J, Ruoppolo M, Orrù S, Caterino M, Kivirikko KI, Koivunen P. Silvennoinen L, et al. J Biol Chem. 2004 Apr 2;279(14):13607-15. doi: 10.1074/jbc.M313054200. Epub 2004 Jan 19. J Biol Chem. 2004. PMID: 14732712 - ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing substrate-partner associations.
Maattanen P, Kozlov G, Gehring K, Thomas DY. Maattanen P, et al. Biochem Cell Biol. 2006 Dec;84(6):881-9. doi: 10.1139/o06-186. Biochem Cell Biol. 2006. PMID: 17215875 Review. - Crystal structure of the bb' domains of the protein disulfide isomerase ERp57.
Kozlov G, Maattanen P, Schrag JD, Pollock S, Cygler M, Nagar B, Thomas DY, Gehring K. Kozlov G, et al. Structure. 2006 Aug;14(8):1331-9. doi: 10.1016/j.str.2006.06.019. Structure. 2006. PMID: 16905107 - In vitro assays of the functions of calnexin and calreticulin, lectin chaperones of the endoplasmic reticulum.
Ireland BS, Niggemann M, Williams DB. Ireland BS, et al. Methods Mol Biol. 2006;347:331-42. doi: 10.1385/1-59745-167-3:331. Methods Mol Biol. 2006. PMID: 17072021 Review.
Cited by
- Enhanced clathrin-dependent endocytosis in the absence of calnexin.
Li HD, Liu WX, Michalak M. Li HD, et al. PLoS One. 2011;6(7):e21678. doi: 10.1371/journal.pone.0021678. Epub 2011 Jul 1. PLoS One. 2011. PMID: 21747946 Free PMC article. - Protein disulfide isomerases contribute differentially to the endoplasmic reticulum-associated degradation of apolipoprotein B and other substrates.
Grubb S, Guo L, Fisher EA, Brodsky JL. Grubb S, et al. Mol Biol Cell. 2012 Feb;23(4):520-32. doi: 10.1091/mbc.E11-08-0704. Epub 2011 Dec 21. Mol Biol Cell. 2012. PMID: 22190736 Free PMC article. - ERp57 is essential for efficient folding of glycoproteins sharing common structural domains.
Jessop CE, Chakravarthi S, Garbi N, Hämmerling GJ, Lovell S, Bulleid NJ. Jessop CE, et al. EMBO J. 2007 Jan 10;26(1):28-40. doi: 10.1038/sj.emboj.7601505. Epub 2006 Dec 14. EMBO J. 2007. PMID: 17170699 Free PMC article. - ERp57/GRP58: a protein with multiple functions.
Turano C, Gaucci E, Grillo C, Chichiarelli S. Turano C, et al. Cell Mol Biol Lett. 2011 Dec;16(4):539-63. doi: 10.2478/s11658-011-0022-z. Epub 2011 Aug 11. Cell Mol Biol Lett. 2011. PMID: 21837552 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous