Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTPâ¢Kap114â¢H2A-H2B complex.
Proc Natl Acad Sci U S A
; 120(29): e2301199120, 2023 Jul 18.
Article
em En
| MEDLINE
| ID: mdl-37450495
ABSTRACT
Previously, we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus. However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9â¢H2A-H2B complex, and formation of the ternary RanGTPâ¢Importin-9â¢H2A-H2B complex facilitates H2A-H2B release to the assembling nucleosome. It was unclear how RanGTP and the cargo H2A-H2B can bind simultaneously to an importin, and how interactions of the three components position H2A-H2B for release. Here, we show cryo-EM structures of Importin-9â¢RanGTP and of its yeast homolog Kap114, including Kap114â¢RanGTP, Kap114â¢H2A-H2B, and RanGTPâ¢Kap114â¢H2A-H2B, to explain how the conserved Kap114 binds H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. In the ternary complex, RanGTP binds to the N-terminal repeats of Kap114 in the same manner as in the Kap114/Importin-9â¢RanGTP complex, and H2A-H2B binds via its acidic patch to the Kap114 C-terminal repeats much like in the Kap114/Importin-9â¢H2A-H2B complex. Ran binds to a different conformation of Kap114 in the ternary RanGTPâ¢Kap114â¢H2A-H2B complex. Here, Kap114 no longer contacts the H2A-H2B surface proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome or to dedicated H2A-H2B chaperones in the nucleus.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nucleossomos
/
Proteínas de Saccharomyces cerevisiae
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2023
Tipo de documento:
Article