title: BECLIN 1-VPS34 COMPLEX ARCHITECTURE: UNDERSTANDING THE NUTS AND BOLTS OF THERAPEUTIC TARGETS.
abstract: Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin 1-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536.
authors.forename: Deanna H
authors.initials: DH
authors.lastname: Morris
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada V6T1Z3.
authors.forename: Calvin K
authors.initials: CK
authors.lastname: Yip
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536 ; Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA ; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Qing Jun
authors.initials: QJ
authors.lastname: Wang
keywords: Beclin 1; CX-MS; EM; Nrbf2; Vps34; complex; drug design; inhibitor; structure