Mapping and engineering the interaction between adiponectin and T-cadherin.
J Biol Chem
; 295(9): 2749-2759, 2020 02 28.
Article
en En
| MEDLINE
| ID: mdl-31915248
ABSTRACT
Adiponectin is a highly abundant protein hormone secreted by adipose tissue. It elicits diverse biological responses, including anti-diabetic, anti-inflammatory, anti-tumor, and anti-atherosclerotic effects. Adiponectin consists of a globular domain and a collagen-like domain, and it occurs in three major oligomeric forms that self-assemble trimers, hexamers, and high-molecular-weight oligomers. Adiponectin has been reported to bind to two seven-transmembrane domain receptors, AdipoR1 and AdipoR2, as well as to the protein T-cadherin, which is highly expressed in the cardiovascular system and binds only the high-molecular-weight form of adiponectin. The molecular mechanisms underlying this specificity remain unclear. Here we used a combination of X-ray crystallography and protein engineering to define the details of adiponectin's interaction with T-cadherin. We found that T-cadherin binds to the globular domain of adiponectin, relying on structural stabilization of this domain by bound metal ions. Moreover, we show that the adiponectin globular domain can be engineered to enhance its binding affinity for T-cadherin. These results help to define the molecular basis for the interaction between adiponectin and T-cadherin, and our engineered globular domain variants may be useful tools for further investigating adiponectin's functions.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ingeniería de Proteínas
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Cadherinas
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Adiponectina
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2020
Tipo del documento:
Article