The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration
Calreticulin is an abundant endoplasmic reticulum resident protein that fulfills at least two basic functions. Firstly, due to its ability to bind monoglucosylated high mannose oligosaccharides, calreticulin is a central component of the folding quality control system of glycoproteins.Onthe other ha...
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2010
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v285_n7_p4544_Giraldo http://hdl.handle.net/20.500.12110/paper_00219258_v285_n7_p4544_Giraldo |
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paper:paper_00219258_v285_n7_p4544_Giraldo2023-06-08T14:43:31Z The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration Basic functions Biophysical techniques C terminus C-terminal domains Calcium addition Calcium binding proteins Calcium concentration Calcium sensors Calreticulin Central component Close proximity Disordered structures Endoplasmic reticulum Intracellular localization Molecular dynamics simulations Ordering effects Primary structures Randomized sequence Sequence specificity Structural information Calcium Concentration (process) Customer satisfaction Molecular dynamics Molecular mechanics Proteins Rigid structures Total quality management Calcium alloys calcium calreticulin article biophysics calcium cell level calcium transport carboxy terminal sequence circular dichroism conformational transition controlled study endoplasmic reticulum molecular dynamics molecular model priority journal protein conformation protein domain protein secondary structure protein structure simulation Animals Calcium Calreticulin Chromatography, Gel Circular Dichroism Fourier Analysis Protein Structure, Secondary Protein Structure, Tertiary Rabbits Calreticulin is an abundant endoplasmic reticulum resident protein that fulfills at least two basic functions. Firstly, due to its ability to bind monoglucosylated high mannose oligosaccharides, calreticulin is a central component of the folding quality control system of glycoproteins.Onthe other hand, thanks to its capacity to bind high amounts of calcium, calreticulin is one of the main calcium buffers in the endoplasmic reticulum. This last activity resides on a highly negatively charged domain located at the C terminus. Interestingly, this domain has been proposed to regulate the intracellular localization of calreticulin. Structural information for this domain is currently scarce. Here we address this issue by employing a combination of biophysical techniques and molecular dynamics simulation. We found that calreticulin C-terminal domain at low calcium concentration displays a disordered structure, whereas calcium addition induces a more rigid and compact conformation. Remarkably, this change develops when calcium concentration varies within a range similar to that taking place in the endoplasmic reticulum upon physiological fluctuations. In addition, a much higher calcium concentration is necessary to attain similar responses in a peptide displaying a randomized sequence of calreticulin C-terminal domain, illustrating the sequence specificity of this effect. Molecular dynamics simulation reveals that this ordering effect is a consequence of the ability of calcium to bring into close proximity residues that lie apart in the primary structure. These results place calreticulin in a new setting in which the protein behaves not only as a calcium-binding protein but as a finely tuned calcium sensor. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v285_n7_p4544_Giraldo http://hdl.handle.net/20.500.12110/paper_00219258_v285_n7_p4544_Giraldo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Basic functions Biophysical techniques C terminus C-terminal domains Calcium addition Calcium binding proteins Calcium concentration Calcium sensors Calreticulin Central component Close proximity Disordered structures Endoplasmic reticulum Intracellular localization Molecular dynamics simulations Ordering effects Primary structures Randomized sequence Sequence specificity Structural information Calcium Concentration (process) Customer satisfaction Molecular dynamics Molecular mechanics Proteins Rigid structures Total quality management Calcium alloys calcium calreticulin article biophysics calcium cell level calcium transport carboxy terminal sequence circular dichroism conformational transition controlled study endoplasmic reticulum molecular dynamics molecular model priority journal protein conformation protein domain protein secondary structure protein structure simulation Animals Calcium Calreticulin Chromatography, Gel Circular Dichroism Fourier Analysis Protein Structure, Secondary Protein Structure, Tertiary Rabbits |
| spellingShingle |
Basic functions Biophysical techniques C terminus C-terminal domains Calcium addition Calcium binding proteins Calcium concentration Calcium sensors Calreticulin Central component Close proximity Disordered structures Endoplasmic reticulum Intracellular localization Molecular dynamics simulations Ordering effects Primary structures Randomized sequence Sequence specificity Structural information Calcium Concentration (process) Customer satisfaction Molecular dynamics Molecular mechanics Proteins Rigid structures Total quality management Calcium alloys calcium calreticulin article biophysics calcium cell level calcium transport carboxy terminal sequence circular dichroism conformational transition controlled study endoplasmic reticulum molecular dynamics molecular model priority journal protein conformation protein domain protein secondary structure protein structure simulation Animals Calcium Calreticulin Chromatography, Gel Circular Dichroism Fourier Analysis Protein Structure, Secondary Protein Structure, Tertiary Rabbits The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration |
| topic_facet |
Basic functions Biophysical techniques C terminus C-terminal domains Calcium addition Calcium binding proteins Calcium concentration Calcium sensors Calreticulin Central component Close proximity Disordered structures Endoplasmic reticulum Intracellular localization Molecular dynamics simulations Ordering effects Primary structures Randomized sequence Sequence specificity Structural information Calcium Concentration (process) Customer satisfaction Molecular dynamics Molecular mechanics Proteins Rigid structures Total quality management Calcium alloys calcium calreticulin article biophysics calcium cell level calcium transport carboxy terminal sequence circular dichroism conformational transition controlled study endoplasmic reticulum molecular dynamics molecular model priority journal protein conformation protein domain protein secondary structure protein structure simulation Animals Calcium Calreticulin Chromatography, Gel Circular Dichroism Fourier Analysis Protein Structure, Secondary Protein Structure, Tertiary Rabbits |
| description |
Calreticulin is an abundant endoplasmic reticulum resident protein that fulfills at least two basic functions. Firstly, due to its ability to bind monoglucosylated high mannose oligosaccharides, calreticulin is a central component of the folding quality control system of glycoproteins.Onthe other hand, thanks to its capacity to bind high amounts of calcium, calreticulin is one of the main calcium buffers in the endoplasmic reticulum. This last activity resides on a highly negatively charged domain located at the C terminus. Interestingly, this domain has been proposed to regulate the intracellular localization of calreticulin. Structural information for this domain is currently scarce. Here we address this issue by employing a combination of biophysical techniques and molecular dynamics simulation. We found that calreticulin C-terminal domain at low calcium concentration displays a disordered structure, whereas calcium addition induces a more rigid and compact conformation. Remarkably, this change develops when calcium concentration varies within a range similar to that taking place in the endoplasmic reticulum upon physiological fluctuations. In addition, a much higher calcium concentration is necessary to attain similar responses in a peptide displaying a randomized sequence of calreticulin C-terminal domain, illustrating the sequence specificity of this effect. Molecular dynamics simulation reveals that this ordering effect is a consequence of the ability of calcium to bring into close proximity residues that lie apart in the primary structure. These results place calreticulin in a new setting in which the protein behaves not only as a calcium-binding protein but as a finely tuned calcium sensor. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. |
| title |
The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration |
| title_short |
The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration |
| title_full |
The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration |
| title_fullStr |
The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration |
| title_full_unstemmed |
The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration |
| title_sort |
structure of calreticulin c-terminal domain is modulated by physiological variations of calcium concentration |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v285_n7_p4544_Giraldo http://hdl.handle.net/20.500.12110/paper_00219258_v285_n7_p4544_Giraldo |
| _version_ |
1768546193290297344 |