The BECN1 N-terminal domain is intrinsically disordered. Issue 3 (3rd March 2016)

• Record Type: Journal Article
• Authors: Lee, Erinna F.; Perugini, Matthew A.; Pettikiriarachchi, Anne; Evangelista, Marco; Keizer, David W.; Yao, Shenggen; Fairlie, W. Douglas
• Is Part Of: Autophagy. Volume 12:Issue 3(2016)
• Page Start: 460
• Page End: 471
• Publication Date: 2016-03-03
• Subjects: autophagy -- BCL2 -- Beclin 1 -- BECN1 -- BH3 domain -- intrinsically disordered protein; nuclear magnetic resonance; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2016.1140292
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: BECN1/Beclin 1 has a critical role in the early stages of autophagosome formation. Recently, structures of its central and C-terminal domains were reported, however, little structural information is available on the N-terminal domain, comprising a third of the protein. This lack of structural information largely stems from the inability to produce this region in a purified form. Here, we describe the expression and purification of the N-terminal domain of BECN1 (residues 1 to 150) and detailed biophysical characterization, including NMR spectroscopy. Combined, our studies demonstrated at the atomic level that the BECN1 N-terminal domain is intrinsically disordered, and apart from the BH3 subdomain, remains disordered following interaction with a binding partner, BCL2L1/BCL-XL . In addition, the BH3 domain α-helix induced upon interaction with BCL2L1 reverts to a disordered state when the complex is dissociated by exposure to a competitive inhibitor. No significant interactions between N- and C-terminal domains were detected.