5K7B

Beclin 2 CCD homodimer

Summary for 5K7B

• Entry DOI: 10.2210/pdb5k7b/pdb
• Descriptor: Beclin-2 (2 entities in total)
• Functional Keywords: coiled-coil domain, autophagy, apoptosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 45201.44

Authors

Su, M.,Sinha, S. (deposition date: 2016-05-25, release date: 2017-03-08, Last modification date: 2024-03-06)

Primary citation

Su, M.,Li, Y.,Wyborny, S.,Neau, D.,Chakravarthy, S.,Levine, B.,Colbert, C.L.,Sinha, S.C.
BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy.
Protein Sci., 26:972-984, 2017

PubMed 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 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.

PubMed: 28218432
DOI: 10.1002/pro.3140

Experimental method

X-RAY DIFFRACTION (2.3 Å)