A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts
Protein assemblies are involved in many important biological processes. Solid-state NMR (SSNMR) spectroscopy is a technique suitable for the structural characterization of samples with high molecular weight and thus can be applied to such assemblies. A significant bottleneck in terms of both effort...
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doaj-bab26ed89607479c91b5bdf3d1f5aed32021-01-02T05:08:16ZengElsevierComputational and Structural Biotechnology Journal2001-03702020-01-0118114124A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contactsDavide Sala0Linda Cerofolini1Marco Fragai2Andrea Giachetti3Claudio Luchinat4Antonio Rosato5Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, ItalyConsorzio Interuniversitario di Risonanze Magnetiche di Metallo Proteine, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, ItalyMagnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy; Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, ItalyConsorzio Interuniversitario di Risonanze Magnetiche di Metallo Proteine, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, ItalyMagnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy; Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, ItalyMagnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy; Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy; Corresponding author at: Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.Protein assemblies are involved in many important biological processes. Solid-state NMR (SSNMR) spectroscopy is a technique suitable for the structural characterization of samples with high molecular weight and thus can be applied to such assemblies. A significant bottleneck in terms of both effort and time required is the manual identification of unambiguous intermolecular contacts. This is particularly challenging for homo-oligomeric complexes, where simple uniform labeling may not be effective. We tackled this challenge by exploiting coevolution analysis to extract information on homo-oligomeric interfaces from NMR-derived ambiguous contacts. After removing the evolutionary couplings (ECs) that are already satisfied by the 3D structure of the monomer, the predicted ECs are matched with the automatically generated list of experimental contacts. This approach provides a selection of potential interface residues that is used directly in monomer–monomer docking calculations. We validated the protocol on tetrameric L-asparaginase II and dimeric Sod1.http://www.sciencedirect.com/science/article/pii/S2001037019303423Homo-oligomersCoevolutionNMREvolutionary constraintsProtein-protein interactionsSolid-state NMR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Davide Sala Linda Cerofolini Marco Fragai Andrea Giachetti Claudio Luchinat Antonio Rosato |
spellingShingle |
Davide Sala Linda Cerofolini Marco Fragai Andrea Giachetti Claudio Luchinat Antonio Rosato A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts Computational and Structural Biotechnology Journal Homo-oligomers Coevolution NMR Evolutionary constraints Protein-protein interactions Solid-state NMR |
author_facet |
Davide Sala Linda Cerofolini Marco Fragai Andrea Giachetti Claudio Luchinat Antonio Rosato |
author_sort |
Davide Sala |
title |
A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts |
title_short |
A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts |
title_full |
A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts |
title_fullStr |
A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts |
title_full_unstemmed |
A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts |
title_sort |
protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and nmr ambiguous contacts |
publisher |
Elsevier |
series |
Computational and Structural Biotechnology Journal |
issn |
2001-0370 |
publishDate |
2020-01-01 |
description |
Protein assemblies are involved in many important biological processes. Solid-state NMR (SSNMR) spectroscopy is a technique suitable for the structural characterization of samples with high molecular weight and thus can be applied to such assemblies. A significant bottleneck in terms of both effort and time required is the manual identification of unambiguous intermolecular contacts. This is particularly challenging for homo-oligomeric complexes, where simple uniform labeling may not be effective. We tackled this challenge by exploiting coevolution analysis to extract information on homo-oligomeric interfaces from NMR-derived ambiguous contacts. After removing the evolutionary couplings (ECs) that are already satisfied by the 3D structure of the monomer, the predicted ECs are matched with the automatically generated list of experimental contacts. This approach provides a selection of potential interface residues that is used directly in monomer–monomer docking calculations. We validated the protocol on tetrameric L-asparaginase II and dimeric Sod1. |
topic |
Homo-oligomers Coevolution NMR Evolutionary constraints Protein-protein interactions Solid-state NMR |
url |
http://www.sciencedirect.com/science/article/pii/S2001037019303423 |
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