Structural highlights
Function
[ERP29_HUMAN] Does not seem to be a disulfide isomerase. Plays an important role in the processing of secretory proteins within the endoplasmic reticulum (ER), possibly by participating in the folding of proteins in the ER. [CLGN_CANLF] Functions during spermatogenesis as a chaperone for a range of client proteins that are important for sperm adhesion onto the egg zona pellucida and for subsequent penetration of the zona pellucida. Required for normal sperm migration from the uterus into the oviduct. Required for normal male fertility. Binds calcium ions (By similarity).
Publication Abstract from PubMed
The lectin chaperones calreticulin (CRT) and calnexin (CNX) contribute to the folding of glycoproteins in the ER by recruiting foldases such as the protein disulfide isomerase ERp57 and the peptidyl prolyl cis-trans isomerase CypB. Recently, CRT was shown to interact with the chaperone ERp29. Here, we show that ERp29 directly binds to the P domain of CNX. Crystal structures of the D domain of ERp29 in complex with the P domains from CRT and calmegin, a tissue-specific CNX homolog, reveal a commonality in the mechanism of binding whereby the tip of the P domain functions as a plurivalent adapter to bind a variety of folding factors. We show that mutation of a single residue, D348 in CNX, abrogates binding to ERp29 as well as ERp57 and CypB. The structural diversity of the accessory factors suggests that these chaperones became specialized for glycoprotein folding through convergent evolution of their P-domain binding sites.
Mapping the ER Interactome: The P Domains of Calnexin and Calreticulin as Plurivalent Adapters for Foldases and Chaperones.,Kozlov G, Munoz-Escobar J, Castro K, Gehring K Structure. 2017 Sep 5;25(9):1415-1422.e3. doi: 10.1016/j.str.2017.07.010. PMID:28877505[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kozlov G, Munoz-Escobar J, Castro K, Gehring K. Mapping the ER Interactome: The P Domains of Calnexin and Calreticulin as Plurivalent Adapters for Foldases and Chaperones. Structure. 2017 Sep 5;25(9):1415-1422.e3. doi: 10.1016/j.str.2017.07.010. PMID:28877505 doi:http://dx.doi.org/10.1016/j.str.2017.07.010
