Macromolecular Crowding by Polyethylene Glycol Reduces Protein Breathing.
J Phys Chem Lett
; 14(10): 2599-2605, 2023 Mar 16.
Article
en En
| MEDLINE
| ID: mdl-36881386
ABSTRACT
Most efforts to understand macromolecular crowding focus on global (i.e., complete) unfolding, but smaller excursions, often called breathing, promote aggregation, which is associated with several diseases and the bane of pharmaceutical and commercial protein production. We used NMR to assess the effects of ethylene glycol (EG) and polyethylene glycols (PEGs) on the structure and stability of the B1 domain of protein G (GB1). Our data show that EG and PEGs stabilize GB1 differently. EG interacts with GB1 more strongly than PEGs, but neither affects the structure of the folded state. EG and 12000 g/mol PEG stabilize GB1 more than PEGs of intermediate size, but EG and smaller PEGs stabilize GB1 enthalpically while the largest PEG acts entropically. Our key finding is that PEGs turn local unfolding into global unfolding, and meta-analysis of published data supports this conclusion. These efforts provide knowledge that can be applied to improve biological drugs and commercial enzymes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Proteínas
Tipo de estudio:
Systematic_reviews
Idioma:
En
Revista:
J Phys Chem Lett
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos