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

Minfei Su, Yue Li, Shane Wyborny, David Neau, Srinivas Chakravarthy, Beth Levine, Christopher L. Colbert, Sangita C. Sinha

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)972-984
Number of pages13
JournalProtein Science
Issue number5
StatePublished - May 1 2017


  • ATG14
  • BECN2
  • BECN2:ATG14 heterodimer
  • autophagy
  • coiled-coil domain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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