Khái niệm cốt lõi
The human TIP60-C complex is a 20-subunit chromatin remodeling assembly that integrates histone exchange and acetylation activities, providing insights into the structural organization and recruitment mechanisms of this key regulator of chromatin dynamics.
Tóm tắt
The content describes the structural and functional characterization of the human TIP60-C chromatin remodeling complex, which is a 20-subunit assembly that integrates two key enzymatic activities: ATP-dependent exchange of histone H2A/H2B for H2A.Z/H2B, and histone acetylation.
The key highlights and insights from the content are:
- The TIP60-C complex has a three-lobed architecture composed of SWR1-like (SWR1L) and NuA4-like (NuA4L) parts, which associate with a TRRAP activator-binding module.
- The large EP400 subunit harbors the ATPase motor, traverses the junction between SWR1L and NuA4L, and constitutes the scaffold of the three-lobed architecture.
- The NuA4L part is significantly rearranged compared to its yeast counterpart, and the TRRAP subunit is flexibly tethered to NuA4L, in contrast to its robust connection in the yeast NuA4 complex.
- A modeled nucleosome bound to the SWR1L part, supported by activity tests, suggests that some aspects of the histone exchange mechanism diverge from the yeast example.
- The fixed actin module, the flexibility of TRRAP, and the weak effect of extra-nucleosomal DNA on exchange activity lead to a different, activator-based mode of recruitment of the TIP60-C complex to chromatin.
Thống kê
The human TIP60-C complex is a 20-subunit assembly.
The structure of the TIP60-C complex was determined at a resolution of 2.4-3.3 Å.
Trích dẫn
"How these activities are merged in humans into one super-complex and what this association entails for their structure, mechanism and recruitment to chromatin is unknown."
"A modeled nucleosome bound to SWR1L, supported by activity tests, suggests that some aspects of the histone exchange mechanism diverge from the yeast example."