Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi
Proteins may adopt diverse conformations during their folding in vivo, ranging from extended chains when they emerge from the ribosome to compact intermediates near the end of the folding process. Accordingly, a variety of chaperones and folding assisting enzymes have evolved to deal with this diver...
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2011
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paper:paper_01666851_v175_n2_p112_Labriola2023-06-08T15:16:01Z Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi BiP Calreticulin Glycoprotein folding quality control Trypanosome cruzi calreticulin glucose regulated protein 78 glycoprotein proteinase unclassified drug uridine diphosphate glc:glycoprotein glucosyltransferase article lysosome molecular interaction mutant nonhuman priority journal protein conformation protein folding Trypanosoma cruzi Calreticulin Cysteine Endopeptidases HSP70 Heat-Shock Proteins Models, Biological Models, Chemical Protein Folding Protozoan Proteins Trypanosoma cruzi Trypanosoma cruzi Proteins may adopt diverse conformations during their folding in vivo, ranging from extended chains when they emerge from the ribosome to compact intermediates near the end of the folding process. Accordingly, a variety of chaperones and folding assisting enzymes have evolved to deal with this diversity. Chaperone selection by a particular substrate depends on the structural features of its folding intermediates. In addition, this process may be modulated by competitive effects between chaperones. Here we address this issue by using TcrCATL as model substrate. TcrCATL is an abundant Trypanosoma cruzi lysosomal protease and it was the first identified endogenous UDP-Glc:glycoprotein glucosyltransferase (UGGT) substrate. We found that TcrCATL associated sequentially with BiP and calreticulin (CRT) during its folding process. Early, extended conformations were bound to BiP, while more advanced and compact folding intermediates associated to CRT. The interaction between TcrCATL and CRT was impeded by deletion of the UGGT-encoding gene but, similarly to what was observed in wild type cells, in mutant cells TcrCATL associated to BiP only when displaying extended conformations. The absence of TcrCATL-CRT interactions in UGGT null cells resulted in a drastic reduction of TcrCATL folding efficiency and triggered the aggregation of TcrCATL through intermolecular disulfide bonds. These observations show that BiP and CRT activities complement each other to supervise a complete and efficient TcrCATL folding process. The present report provides further evidence on the early evolutionary acquisition of the basic tenets of the N-glycan dependent quality control mechanism of glycoprotein folding. © 2010 Elsevier B.V. All rights reserved. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01666851_v175_n2_p112_Labriola http://hdl.handle.net/20.500.12110/paper_01666851_v175_n2_p112_Labriola |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
BiP Calreticulin Glycoprotein folding quality control Trypanosome cruzi calreticulin glucose regulated protein 78 glycoprotein proteinase unclassified drug uridine diphosphate glc:glycoprotein glucosyltransferase article lysosome molecular interaction mutant nonhuman priority journal protein conformation protein folding Trypanosoma cruzi Calreticulin Cysteine Endopeptidases HSP70 Heat-Shock Proteins Models, Biological Models, Chemical Protein Folding Protozoan Proteins Trypanosoma cruzi Trypanosoma cruzi |
| spellingShingle |
BiP Calreticulin Glycoprotein folding quality control Trypanosome cruzi calreticulin glucose regulated protein 78 glycoprotein proteinase unclassified drug uridine diphosphate glc:glycoprotein glucosyltransferase article lysosome molecular interaction mutant nonhuman priority journal protein conformation protein folding Trypanosoma cruzi Calreticulin Cysteine Endopeptidases HSP70 Heat-Shock Proteins Models, Biological Models, Chemical Protein Folding Protozoan Proteins Trypanosoma cruzi Trypanosoma cruzi Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi |
| topic_facet |
BiP Calreticulin Glycoprotein folding quality control Trypanosome cruzi calreticulin glucose regulated protein 78 glycoprotein proteinase unclassified drug uridine diphosphate glc:glycoprotein glucosyltransferase article lysosome molecular interaction mutant nonhuman priority journal protein conformation protein folding Trypanosoma cruzi Calreticulin Cysteine Endopeptidases HSP70 Heat-Shock Proteins Models, Biological Models, Chemical Protein Folding Protozoan Proteins Trypanosoma cruzi Trypanosoma cruzi |
| description |
Proteins may adopt diverse conformations during their folding in vivo, ranging from extended chains when they emerge from the ribosome to compact intermediates near the end of the folding process. Accordingly, a variety of chaperones and folding assisting enzymes have evolved to deal with this diversity. Chaperone selection by a particular substrate depends on the structural features of its folding intermediates. In addition, this process may be modulated by competitive effects between chaperones. Here we address this issue by using TcrCATL as model substrate. TcrCATL is an abundant Trypanosoma cruzi lysosomal protease and it was the first identified endogenous UDP-Glc:glycoprotein glucosyltransferase (UGGT) substrate. We found that TcrCATL associated sequentially with BiP and calreticulin (CRT) during its folding process. Early, extended conformations were bound to BiP, while more advanced and compact folding intermediates associated to CRT. The interaction between TcrCATL and CRT was impeded by deletion of the UGGT-encoding gene but, similarly to what was observed in wild type cells, in mutant cells TcrCATL associated to BiP only when displaying extended conformations. The absence of TcrCATL-CRT interactions in UGGT null cells resulted in a drastic reduction of TcrCATL folding efficiency and triggered the aggregation of TcrCATL through intermolecular disulfide bonds. These observations show that BiP and CRT activities complement each other to supervise a complete and efficient TcrCATL folding process. The present report provides further evidence on the early evolutionary acquisition of the basic tenets of the N-glycan dependent quality control mechanism of glycoprotein folding. © 2010 Elsevier B.V. All rights reserved. |
| title |
Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi |
| title_short |
Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi |
| title_full |
Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi |
| title_fullStr |
Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi |
| title_full_unstemmed |
Functional cooperation between BiP and calreticulin in the folding maturation of a glycoprotein in Trypanosoma cruzi |
| title_sort |
functional cooperation between bip and calreticulin in the folding maturation of a glycoprotein in trypanosoma cruzi |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01666851_v175_n2_p112_Labriola http://hdl.handle.net/20.500.12110/paper_01666851_v175_n2_p112_Labriola |
| _version_ |
1768543176355741696 |