Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation.
J Biol Chem
; 294(8): 2949-2960, 2019 02 22.
Article
em En
| MEDLINE
| ID: mdl-30635401
ABSTRACT
Protein disulfide bonds link pairs of cysteine residues in polypeptide chains. Many of these bonds serve a purely structural or energetic role, but a growing subset of cleavable disulfide bonds has been shown to control the function of the mature protein in which they reside. These allosteric disulfides and the factors that cleave these bonds are being identified across biological systems and life forms and have been shown to control hemostasis, the immune response, and viral infection in mammals. The discovery of these functional disulfides and a rationale for their facile nature has been aided by the emergence of a conformational signature for allosteric bonds. This post-translational modification mostly occurs extracellularly, making these chemical events prime drug targets. Indeed, a membrane-impermeable inhibitor of one of the cleaving factors is currently being trialed as an antithrombotic agent in cancer patients. Allosteric disulfides are firmly established as a sophisticated means by which a protein's shape and function can be altered; however, the full scope of this biological regulation will not be realized without new tools and techniques to study this regulation and innovative ways of targeting it.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Viroses
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Processamento de Proteína Pós-Traducional
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Hemostasia
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Imunidade
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Proteínas de Neoplasias
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article