7UWF

Human Rix1 sub-complex scaffold

Summary for 7UWF

• Entry DOI: 10.2210/pdb7uwf/pdb
• EMDB information: 26831
• Descriptor: WD repeat-containing protein 18, Modulator of non-genomic activity of estrogen receptor (2 entities in total)
• Functional Keywords: scaffold, complex, wd-repeat, solenoid, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 236808.07

Authors

Gordon, J.,Stanley, R.E. (deposition date: 2022-05-03, release date: 2022-11-02, Last modification date: 2024-06-12)

Primary citation

Gordon, J.,Chapus, F.L.,Viverette, E.G.,Williams, J.G.,Deterding, L.J.,Krahn, J.M.,Borgnia, M.J.,Rodriguez, J.,Warren, A.J.,Stanley, R.E.
Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold.
Nat Commun, 13:6783-6783, 2022

PubMed Abstract: PELP1 (Proline-, Glutamic acid-, Leucine-rich protein 1) is a large scaffolding protein that functions in many cellular pathways including steroid receptor (SR) coactivation, heterochromatin maintenance, and ribosome biogenesis. PELP1 is a proto-oncogene whose expression is upregulated in many human cancers, but how the PELP1 scaffold coordinates its diverse cellular functions is poorly understood. Here we show that PELP1 serves as the central scaffold for the human Rix1 complex whose members include WDR18, TEX10, and SENP3. We reconstitute the mammalian Rix1 complex and identified a stable sub-complex comprised of the conserved PELP1 Rix1 domain and WDR18. We determine a 2.7 Å cryo-EM structure of the subcomplex revealing an interconnected tetrameric assembly and the architecture of PELP1's signaling motifs, including eleven LxxLL motifs previously implicated in SR signaling and coactivation of Estrogen Receptor alpha (ERα) mediated transcription. However, the structure shows that none of these motifs is in a conformation that would support SR binding. Together this work establishes that PELP1 scaffolds the Rix1 complex, and association with WDR18 may direct PELP1's activity away from SR coactivation.

PubMed: 36351913
DOI: 10.1038/s41467-022-34610-0

Experimental method

ELECTRON MICROSCOPY (2.7 Å)