Autophagy, a cellular homeostasis process that degrades and recycles cytosolic contents, is regulated at various stages by protein interactions. BECN1 regulates autophagy through interactions with diverse proteins via binding-induced conformational changes in its intrinsically disordered region (IDR) and flexible domains. Understanding the structure-function relationship of conformational transitions provides a basis for understanding these interactions and may be useful for targeting therapeutics for these proteins. We devised a method to identify IDRs likely to become helical upon binding, even in the absence of known binding partners, and analyzed BECN1 interactions to further understand how bindinginduced conformational changes affect BECN1-mediated autophagy regulation. We showed that the BECN1 coiled-coil domain (CCD) and β-α repeated, autophagy-specific domain (BARAD) share an overlapping helix (OH) region that transiently adopts mutually exclusive packing states and transiently packs against the CCD and BARAD, but predominantly packs against the BARAD in the homodimer, and demonstrated that mutation of OH residues that pack against both domains abrogates starvation-induced up-regulation of autophagy. Our results have important implications for the relative stability of autophagy-inactive and autophagy-active BECN1 complexes. We also attempted to establish the mechanism by which various virus-encoded proteins regulate autophagy. Nef, a critical protein for HIV pathogenesis, interacts with BECN1 BARAD regions that pack against the OH. However, we show that Nef does not appear to interact directly with the BECN1 homodimer, suggesting that packing of the OH against the BARAD may inhibit the Nef interaction. Several anti-apoptotic viral BCL2 (vBCL2) proteins down-regulate autophagy by binding the BECN1 BH3 homology domain (BH3D) and mediating binding-induced helical transitions in the BH3D. Although protein purification issues prevented analysis of Kaposi’s sarcoma herpesvirus (KSHV) vBCL2 interactions, we determined that BHRF1, an Epstein-Barr virus (EBV)-encoded vBCL2, down-regulates autophagy by binding a flexible region of BECN1 that includes the BH3D. Further, we solved the 2.6 Å crystal structure of BHRF1 bound to the BID BH3D, a pro-apoptotic BCL2, and showed that the BID BH3D binds ~400-times tighter than the BECN1 BH3D to BHRF1 and inhibits BHRF1-mediated downregulation of autophagy. Together, our studies highlight the importance of binding-induced conformational changes in proteins that regulate autophagy.