5k7b | pdb_00005k7b
Beclin 2 CCD homodimer
Structural highlights
Function[BECN2_HUMAN] Involved in 2 distinct lysosomal degradation pathways: acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover. Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1.[1] Publication Abstract from PubMedATG14 binding to BECN/Beclin homologs is essential for autophagy, a critical catabolic homeostasis pathway. Here we show that the alpha-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. BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy.,Su M, Li Y, Wyborny S, Neau D, Chakravarthy S, Levine B, Colbert CL, Sinha SC Protein Sci. 2017 Feb 20. doi: 10.1002/pro.3140. PMID:28218432[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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