title: Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway.
abstract: The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway.
authors: From the ‡CNRS UMR 8126, Université Paris-Sud 11, Institut Gustave Roussy, 114, rue Edouard Vaillant, 94805, Villejuif, France;
authors: Romain
authors: R
authors: Algret
authors: §Laboratory of Cellular and Structural Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065;
authors: Javier
authors: J
authors: Fernandez-Martinez
authors: ¶Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065;
authors: Yi
authors: Y
authors: Shi
authors: ‖Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, California 94158-2330.
authors: Seung Joong
authors: SJ
authors: Kim
authors: ‖Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, California 94158-2330.
authors: Riccardo
authors: R
authors: Pellarin
authors: ‖Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, California 94158-2330.
authors: Peter
authors: P
authors: Cimermancic
authors: From the ‡CNRS UMR 8126, Université Paris-Sud 11, Institut Gustave Roussy, 114, rue Edouard Vaillant, 94805, Villejuif, France;
authors: Emilie
authors: E
authors: Cochet
authors: ‖Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, California 94158-2330.
authors: Andrej
authors: A
authors: Sali
authors: ¶Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065;
authors: Brian T
authors: BT
authors: Chait
authors: §Laboratory of Cellular and Structural Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065;
authors: Michael P
authors: MP
authors: Rout
authors: From the ‡CNRS UMR 8126, Université Paris-Sud 11, Institut Gustave Roussy, 114, rue Edouard Vaillant, 94805, Villejuif, France; svetlana.dokudovskaya@igr.fr.
authors: Svetlana
authors: S
authors: Dokudovskaya
mesh_terms: D001343:Autophagy / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D008928:Mitochondria / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D009584:Nitrogen