Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein

Proceedings of the National Academy of Sciences of the United States of America
Krzysztof B Wicher, Erik Fries

Abstract

Many secretory proteins are synthesized as proforms that become biologically active through a proteolytic cleavage in the trans-Golgi complex or at a later stage in the secretory pathway. Haptoglobin (Hp) is unusual in that it is cleaved in the endoplasmic reticulum before it enters the Golgi. Here, we present evidence that the recently discovered complement C1r-like protein (C1r-LP) mediates this cleavage. C1r-LP has not previously been shown to possess proteolytic activity, despite its homology to trypsin-like Ser proteinases. We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction. C1r-LP showed specificity for proHp, in that it did not cleave the proform of complement C1s, a protein similar to Hp particularly around the cleavage site. C1r-LP accounts for at least part of the endogenous pro...Continue Reading

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Citations

Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Amit TripathiAlessio Fasano
Aug 5, 2009·Antioxidants & Redox Signaling·Krzysztof B Wicher, Erik Fries
Aug 8, 2009·Antioxidants & Redox Signaling·Marianne Jensby NielsenSøren Kragh Moestrup
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Krzysztof B Wicher, Erik Fries
Aug 8, 2007·Protein Expression and Purification·Alexander HillarHugh O Brodovich
Jul 24, 2007·Blood Cells, Molecules & Diseases·Audrey FayeSophie Vaulont
Jan 31, 2007·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Shiori TsuboneHiroki Abe
Jun 27, 2012·Annals of the New York Academy of Sciences·Alessio Fasano
Dec 16, 2011·Environmental and Molecular Mutagenesis·Bryan A BassigQing Lan
Jul 19, 2005·Molecular and Biochemical Parasitology·Michael Klemba, Daniel E Goldberg
Oct 22, 2008·The Journal of General Virology·Josephine S GnanandarajahMichael P Murtaugh
Sep 22, 2016·Antioxidants & Redox Signaling·Christian Brix Folsted AndersenSøren Kragh Moestrup
Jun 22, 2011·Electrophoresis·Kongsak BoonyapranaiShui-Tien Chen
Nov 15, 2006·The Journal of Biological Chemistry·Marianne Jensby NielsenSøren Kragh Moestrup
May 12, 2019·Digestive Diseases and Sciences·Francesco Valitutti, Alessio Fasano
Jun 17, 2006·Blood·Marianne Jensby NielsenSøren Kragh Moestrup
Sep 9, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anthony K RedmondHelen Dooley
Jun 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sem TamaraAlbert J R Heck
Nov 6, 2004·The Biochemical Journal·Christina LigoudistianouJohn E Volanakis
Feb 11, 2021·International Journal of Molecular Sciences·Stefanie A I WeissDieter E Jenne
Jan 26, 2020·Analytical Biochemistry·Koichi MorishitaEiji Miyoshi
Jul 15, 2020·Molecular Aspects of Medicine·Alessandra di MasiPaolo Ascenzi
Apr 17, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·S N Naryzhny, O K Legina
Jul 23, 2021·Molecular Pharmaceutics·Raphael M BuzziDominik J Schaer
Aug 24, 2021·Biochemistry (Moscow) Supplement. Series B, Biomedical Chemistry·S N Naryzny, O K Legina

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