Structural highlights
Function
[BECN1_RAT] Plays a central role in autophagy. Required for the abcission step in cytokinesis. May play a role in antiviral host defense (By similarity).
Publication Abstract from PubMed
Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1-Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer-heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1-VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy.
Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG.,Li X, He L, Che KH, Funderburk SF, Pan L, Pan N, Zhang M, Yue Z, Zhao Y Nat Commun. 2012 Feb 7;3:662. doi: 10.1038/ncomms1648. PMID:22314358[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li X, He L, Che KH, Funderburk SF, Pan L, Pan N, Zhang M, Yue Z, Zhao Y. Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG. Nat Commun. 2012 Feb 7;3:662. doi: 10.1038/ncomms1648. PMID:22314358 doi:http://dx.doi.org/10.1038/ncomms1648
