4CQO

Structure of the human CNOT1 superfamily homology domain in complex with a Nanos1 peptide

Summary for 4CQO

• Entry DOI: 10.2210/pdb4cqo/pdb
• Descriptor: CCR4-NOT TRANSCRIPTION COMPLEX SUBUNIT 1, NANOS HOMOLOG 1 (3 entities in total)
• Functional Keywords: gene regulation, translation, deadenylation, translational repression, protein complex, development, short linear motif
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, P-body: A5YKK6; Cytoplasm, perinuclear region: Q8WY41
• Total number of polymer chains: 4
• Total formula weight: 126892.52

Authors

Raisch, T.,Jonas, S.,Weichenrieder, O.,Bhandari, D.,Izaurralde, E. (deposition date: 2014-02-21, release date: 2014-04-23, Last modification date: 2023-12-20)

Primary citation

Bhandari, D.,Raisch, T.,Weichenrieder, O.,Jonas, S.,Izaurralde, E.
Structural Basis for the Nanos-Mediated Recruitment of the Ccr4-not Complex and Translational Repression
Genes Dev., 28:888-, 2014

PubMed Abstract: The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function.

PubMed: 24736845
DOI: 10.1101/GAD.237289.113

Experimental method

X-RAY DIFFRACTION (2.8 Å)