Unfolding and Aggregation Pathways of Variable Domains from Immunoglobulin Light Chains.
Biochemistry
; 62(5): 1000-1011, 2023 03 07.
Article
en En
| MEDLINE
| ID: mdl-36802343
ABSTRACT
Light chain amyloidosis is the most common form of systemic amyloidosis. This disease is caused by the formation and deposition of amyloid fibers made from immunoglobulin light chains. Environmental conditions such as pH and temperature can affect protein structure and induce the development of these fibers. Several studies have shed light on the native state, stability, dynamics, and final amyloid state of these proteins; however, the initiation process and the fibril formation pathway remain poorly understood structurally and kinetically. To study this, we analyzed the unfolding and aggregation process of the 6aJL2 protein under acidic conditions, with temperature changes, and upon mutation, using biophysical and computational techniques. Our results suggest that the differences in amyloidogenicity displayed by 6aJL2 under these conditions are caused by traversing different aggregation pathways, including unfolded intermediates and the formation of oligomers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cadenas Ligeras de Inmunoglobulina
/
Amiloidosis
Límite:
Humans
Idioma:
En
Revista:
Biochemistry
Año:
2023
Tipo del documento:
Article
País de afiliación:
México
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA