BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy

Protein Sci. 2017 May;26(5):972-984. doi: 10.1002/pro.3140. Epub 2017 Mar 12.


ATG14 binding to BECN/Beclin homologs is essential for autophagy, a critical catabolic homeostasis pathway. Here, we show that the α-helical, coiled-coil domain (CCD) of BECN2, a recently identified mammalian BECN1 paralog, forms an antiparallel, curved homodimer with seven pairs of nonideal packing interactions, while the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer stabilized by multiple, conserved polar interactions. Compared to BECN1, the BECN2 CCD forms a weaker homodimer, but binds more tightly to the ATG14 CCD. Mutation of nonideal BECN2 interface residues to more ideal pairs improves homodimer self-association and thermal stability. Unlike BECN1, all BECN2 CCD mutants bind ATG14, although more weakly than wild type. Thus, polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. These structure-based mechanistic differences in BECN1 and BECN2 homodimerization and heterodimerization likely dictate competitive ATG14 recruitment.

Keywords: ATG14; BECN2; BECN2:ATG14 heterodimer; autophagy; coiled-coil domain.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / chemistry*
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Autophagy*
  • Autophagy-Related Proteins / chemistry*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Protein Structure, Secondary


  • ATG14 protein, human
  • Adaptor Proteins, Vesicular Transport
  • Autophagy-Related Proteins
  • BECN2 protein, human
  • Intracellular Signaling Peptides and Proteins