Title
BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy
Author
Minfei Su, Yue Li, Shane Wyborny, David Neau, Srinivas Chakravarthy, Beth Levine, Christopher L. Colbert, Sangita C. Sinha
Year
2017
Journal
Protein Science
Abstract
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 anti-parallel, curved homodimer with seven pairs of non-ideal 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 non-ideal 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. This article is protected by copyright. All rights reserved.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Biochemistry