Molecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway

Mol Cell Proteomics. 2014 Nov;13(11):2855-70. doi: 10.1074/mcp.M114.039388. Epub 2014 Jul 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Gene Expression Regulation, Fungal
  • Mitochondria / metabolism
  • Nitrogen / metabolism
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Nuclear Pore Complex Proteins / ultrastructure
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*

Substances

  • Nuclear Pore Complex Proteins
  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Transcription Factors
  • Nitrogen

Associated data

  • PDB/2PM7
  • PDB/3F3F
  • PDB/3TW8