Structures of the ApoL1 and ApoL2 N-terminal domains reveal a non-classical four-helix bundle motif.
Commun Biol
; 4(1): 916, 2021 07 27.
Article
en En
| MEDLINE
| ID: mdl-34316015
ABSTRACT
Apolipoprotein L1 (ApoL1) is a circulating innate immunity protein protecting against trypanosome infection. However, two ApoL1 coding variants are associated with a highly increased risk of chronic kidney disease. Here we present X-ray and NMR structures of the N-terminal domain (NTD) of ApoL1 and of its closest relative ApoL2. In both proteins, four of the five NTD helices form a four-helix core structure which is different from the classical four-helix bundle and from the pore-forming domain of colicin A. The reactivity with a conformation-specific antibody and structural models predict that this four-helix motif is also present in the NTDs of ApoL3 and ApoL4, suggesting related functions within the small ApoL family. The long helix 5 of ApoL1 is conformationally flexible and contains the BH3-like region. This BH3-like α-helix resembles true BH3 domains only in sequence and structure but not in function, since it does not bind to the pro-survival members of the Bcl-2 family, suggesting a Bcl-2-independent role in cytotoxicity. These findings should expedite a more comprehensive structural and functional understanding of the ApoL immune protein family.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Dominios Proteicos
/
Apolipoproteínas L
/
Apolipoproteína L1
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos