The endoplasmic reticulum HSP40 co-chaperone ERdj3/DNAJB11 assembles and functions as a tetramer.
EMBO J
; 36(15): 2296-2309, 2017 08 01.
Article
en En
| MEDLINE
| ID: mdl-28655754
ABSTRACT
ERdj3/DNAJB11 is an endoplasmic reticulum (ER)-targeted HSP40 co-chaperone that performs multifaceted functions involved in coordinating ER and extracellular proteostasis. Here, we show that ERdj3 assembles into a native tetramer that is distinct from the dimeric structure observed for other HSP40 co-chaperones. An electron microscopy structural model of full-length ERdj3 shows that these tetramers are arranged as a dimer of dimers formed by distinct inter-subunit interactions involving ERdj3 domain II and domain III Targeted deletion of residues 175-190 within domain II renders ERdj3 a stable dimer that is folded and efficiently secreted from mammalian cells. This dimeric ERdj3 shows impaired substrate binding both in the ER and extracellular environments and reduced interactions with the ER HSP70 chaperone BiP. Furthermore, we show that overexpression of dimeric ERdj3 exacerbates ER stress-dependent reductions in the secretion of a destabilized, aggregation-prone protein and increases its accumulation as soluble oligomers in extracellular environments. These results reveal ERdj3 tetramerization as an important structural framework for ERdj3 functions involved in coordinating ER and extracellular proteostasis in the presence and absence of ER stress.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Retículo Endoplásmico
/
Proteínas del Choque Térmico HSP40
/
Multimerización de Proteína
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos