Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation
The polypeptide backbone of proteins is held together by two main types of covalent bonds: the peptide bonds that link the amino acid residues and the disulfide bonds that link pairs of cysteine amino acids. Disulfide bonds form as a protein folds in the cell and formation was assumed to be complete...
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doaj-06c95a440c4148b6841f90f209f236aa2020-12-05T00:03:32ZengMDPI AGMolecules1420-30492020-12-01255729572910.3390/molecules25235729Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond FormationPhilip J. Hogg0The Centenary Institute, Camperdown, NSW 2050, AustraliaThe polypeptide backbone of proteins is held together by two main types of covalent bonds: the peptide bonds that link the amino acid residues and the disulfide bonds that link pairs of cysteine amino acids. Disulfide bonds form as a protein folds in the cell and formation was assumed to be complete when the mature protein emerges. This is not the case for some secreted human blood proteins. The blood clotting protein, fibrinogen, and the protease inhibitor, α2-macroglobulin, exist in multiple disulfide-bonded or covalent states in the circulation. Thousands of different states are predicted assuming no dependencies on disulfide bond formation. In this study, probabilities for disulfide bond formation are employed to estimate numbers of covalent states of a model polypeptide with reference to α2-macroglobulin. When disulfide formation is interdependent in a protein, the number of covalent states is greatly reduced. Theoretical estimates of the number of states will aid the conceptual and experimental challenges of investigating multiple disulfide-bonded states of a protein.https://www.mdpi.com/1420-3049/25/23/5729disulfide bondcystinecysteineprobabilityallosteric |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Philip J. Hogg |
spellingShingle |
Philip J. Hogg Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation Molecules disulfide bond cystine cysteine probability allosteric |
author_facet |
Philip J. Hogg |
author_sort |
Philip J. Hogg |
title |
Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation |
title_short |
Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation |
title_full |
Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation |
title_fullStr |
Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation |
title_full_unstemmed |
Multiple Disulfide-Bonded States of Native Proteins: Estimate of Number Using Probabilities of Disulfide Bond Formation |
title_sort |
multiple disulfide-bonded states of native proteins: estimate of number using probabilities of disulfide bond formation |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-12-01 |
description |
The polypeptide backbone of proteins is held together by two main types of covalent bonds: the peptide bonds that link the amino acid residues and the disulfide bonds that link pairs of cysteine amino acids. Disulfide bonds form as a protein folds in the cell and formation was assumed to be complete when the mature protein emerges. This is not the case for some secreted human blood proteins. The blood clotting protein, fibrinogen, and the protease inhibitor, α2-macroglobulin, exist in multiple disulfide-bonded or covalent states in the circulation. Thousands of different states are predicted assuming no dependencies on disulfide bond formation. In this study, probabilities for disulfide bond formation are employed to estimate numbers of covalent states of a model polypeptide with reference to α2-macroglobulin. When disulfide formation is interdependent in a protein, the number of covalent states is greatly reduced. Theoretical estimates of the number of states will aid the conceptual and experimental challenges of investigating multiple disulfide-bonded states of a protein. |
topic |
disulfide bond cystine cysteine probability allosteric |
url |
https://www.mdpi.com/1420-3049/25/23/5729 |
work_keys_str_mv |
AT philipjhogg multipledisulfidebondedstatesofnativeproteinsestimateofnumberusingprobabilitiesofdisulfidebondformation |
_version_ |
1724400143210381312 |