The human CNOT1-CNOT10-CNOT11 complex forms a structural platform for protein-protein interactions

Fabienne Mauxion (1) , Jérôme Basquin (2) , Sevim Ozgur (2) , Marion Rame (3) , Jana Albrecht (2) , Ingmar Schäfer (2) , Bertrand Séraphin (1) , Elena Conti (2)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 MPIB - Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry
3 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie

The evolutionary conserved CCR4-NOT complex functions in the cytoplasm as the main mRNA deadenylase in both constitutive mRNA turnover and regulated mRNA decay pathways. The versatility of this complex is underpinned by its modular multi-subunit organization, with distinct structural modules actuating different functions. The structure and function of all modules are known, except for that of the N-terminal module. Using different structural approaches, we obtained high-resolution data revealing the architecture of the human N-terminal module composed of CNOT1, CNOT10, and CNOT11. The structure shows how two helical domains of CNOT1 sandwich CNOT10 and CNOT11, leaving the most conserved domain of CNOT11 protruding into solvent as an antenna. We discovered that GGNBP2, a protein identified as a tumor suppressor and spermatogenic factor, is a conserved interacting partner of the CNOT11 antenna domain. Structural and biochemical analyses thus pinpoint the N-terminal CNOT1-CNOT10-CNOT11 module as a conserved protein-protein interaction platform.

Mots clés: protein-protein interactions; GGNBP2; X-ray crystallography; cryo-EM; AlphaFold; CCR4-NOT complex; mRNA decay; deadenylation

Domaines: Biologie structurale [q-bio.BM]

Fabienne Mauxion, Jérôme Basquin, Sevim Ozgur, Marion Rame, Jana Albrecht, et al.. The human CNOT1-CNOT10-CNOT11 complex forms a structural platform for protein-protein interactions. Cell Reports, 2023, 42 (1), pp.111902. ⟨10.1016/j.celrep.2022.111902⟩. ⟨hal-04179547⟩