Conformational States of the Cytoprotective Protein Bcl-xL. Biophys J 2020 Oct 06;119(7):1324-1334
Date
09/06/2020Pubmed ID
32888404Pubmed Central ID
PMC7567986DOI
10.1016/j.bpj.2020.08.014Scopus ID
2-s2.0-85090205653 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Bcl-xL is a major inhibitor of apoptosis, a fundamental homeostatic process of programmed cell death that is highly conserved across evolution. Because it plays prominent roles in cancer, Bcl-xL is a major target for anticancer therapy and for studies aimed at understanding its structure and activity. Although Bcl-xL is active primarily at intracellular membranes, most studies have focused on soluble forms of the protein lacking both the membrane-anchoring C-terminal tail and the intrinsically disordered loop, and this has resulted in a fragmented view of the protein's biological activity. Here, we describe the conformation of full-length Bcl-xL. Using NMR spectroscopy, molecular dynamics simulations, and isothermal titration calorimetry, we show how the three structural elements affect the protein's structure, dynamics, and ligand-binding activity in both its soluble and membrane-anchored states. The combined data provide information about the molecular basis for the protein's functionality and a view of its complex molecular mechanisms.
Author List
Ryzhov P, Tian Y, Yao Y, Bobkov AA, Im W, Marassi FMAuthor
Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisMagnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Protein Conformation
bcl-X Protein
