Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG.

Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that ...
forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1-Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer-heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1-VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy.
Mesh Terms:
Adaptor Proteins, Vesicular Transport, Amino Acid Motifs, Amino Acid Sequence, Apoptosis Regulatory Proteins, Autophagy, Autophagy-Related Proteins, Beclin-1, Class III Phosphatidylinositol 3-Kinases, Crystallography, X-Ray, Dimerization, HEK293 Cells, Humans, Membrane Proteins, Models, Molecular, Molecular Conformation, Molecular Sequence Data, Mutation, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Static Electricity, Temperature, Tumor Suppressor Proteins
Nat Commun
Date: Feb. 07, 2012
Download Curated Data For This Publication
220431
Switch View:
  • Interactions 4