6f46 | pdb_00006f46
Structure of the transmembrane helix of BclxL in phospholipid nanodiscs
Structural highlights
FunctionB2CL1_HUMAN Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.[1] [2] Isoform Bcl-X(S) promotes apoptosis.[3] [4] Publication Abstract from PubMedStructural studies on membrane-anchored proteins containing a transmembrane (TM) helix have been hampered by difficulties in producing these proteins in a natively folded form. Detergents that are required to solubilize the hydrophobic TM helix usually destabilize the soluble domain. Thus, TM helices are removed for structural studies, which neglects the pivotal role of a membrane on protein function. This work presents a versatile strategy for the production of this protein class attached to phospholipid nanodiscs. By inserting the TM-helix into nanodiscs and a subsequent SortaseA-mediated ligation of the soluble domain, membrane-anchored BclxL could be obtained in a folded conformation. This strategy is suitable for high-resolution structure determination as well as for probing membrane location by NMR. This method will be applicable to a wide range of membrane-anchored proteins and will be useful to decipher their functional role in a native membrane environment. Production and Structural Analysis of Membrane-Anchored Proteins in Phospholipid Nanodiscs.,Raltchev K, Pipercevic J, Hagn F Chemistry. 2018 Apr 11;24(21):5493-5499. doi: 10.1002/chem.201800812. Epub 2018, Mar 23. PMID:29457664[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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