6X7I

Structure of the C-terminal domain of BCL-XL in membrane

Summary for 6X7I

• Entry DOI: 10.2210/pdb6x7i/pdb
• NMR Information: BMRB: 30757
• Descriptor: Bcl-2-like protein 1 (1 entity in total)
• Functional Keywords: anti-apoptotic, bcl-2, membrane, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 3174.72

Authors

Yao, Y.,Tian, Y.,Marassi, F.M. (deposition date: 2020-05-30, release date: 2020-07-01, Last modification date: 2024-05-15)

Primary citation

Ryzhov, P.,Tian, Y.,Yao, Y.,Bobkov, A.A.,Im, W.,Marassi, F.M.
Conformational States of the Cytoprotective Protein Bcl-xL.
Biophys.J., 119:1324-1334, 2020

PubMed Abstract: 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.

PubMed: 32888404
DOI: 10.1016/j.bpj.2020.08.014

Experimental method

SOLID-STATE NMR
SOLUTION NMR