Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1.
Nucleic Acids Res
; 50(1): 522-535, 2022 01 11.
Article
en En
| MEDLINE
| ID: mdl-34904671
ABSTRACT
The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified 'ß-clasp' structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ARN
/
Proteínas de Unión al ARN
/
Proteínas de Unión al ADN
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia