BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy: BECN2 CCD Structure and Interaction with ATG14

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

doi:10.1002/pro.3140

BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy: BECN2 CCD Structure and Interaction with ATG14

Journal Article · Sun Mar 12 04:00:00 EDT 2017 · Protein Science

DOI:https://doi.org/10.1002/pro.3140· OSTI ID:1418032

Su, Minfei ^[1]; Li, Yue ^[1]; Wyborny, Shane ^[1]; Neau, David ^[2]; Chakravarthy, Srinivas ^[3]; Levine, Beth ^[4]; Colbert, Christopher L. ^[1]; Sinha, Sangita C. ^[1]

Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050
Department of Chemistry and Chemical Biology, Cornell University, Northeastern Collaborative Access Team, Argonne National Laboratory, Argonne Illinois 60439
Biophysics Collaborative Access Team/Illinois Institute of Technology, Advanced Photon Source, Argonne National Laboratory, Argonne Illinois 60439
Center for Autophagy Research, Department of Internal Medicine and Howard Hughes Medical Research Institute, University of Texas Southwestern Medical Center, Dallas Texas 75390

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.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIH

OSTI ID:: 1418032

Journal Information:: Protein Science, Journal Name: Protein Science Journal Issue: 5 Vol. 26; ISSN 0961-8368

Publisher:: The Protein Society

Country of Publication:: United States

Language:: ENGLISH

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