5W5Z

Crystal structure of BAXP168G in complex with an activating antibody at high resolution

Summary for 5W5Z

• Entry DOI: 10.2210/pdb5w5z/pdb
• Descriptor: 3C10 Fab light chain, 3C10 Fab heavy chain, Apoptosis regulator BAX, ... (8 entities in total)
• Functional Keywords: fab, bax activation, unfolding, apoptosis
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 67603.06

Authors

Robin, A.Y.,Colman, P.M.,Czabotar, P.E. (deposition date: 2017-06-16, release date: 2018-06-27, Last modification date: 2024-10-23)

Primary citation

Robin, A.Y.,Iyer, S.,Birkinshaw, R.W.,Sandow, J.,Wardak, A.,Luo, C.S.,Shi, M.,Webb, A.I.,Czabotar, P.E.,Kluck, R.M.,Colman, P.M.
Ensemble Properties of Bax Determine Its Function.
Structure, 26:1346-, 2018

PubMed Abstract: BAX and BAK are essential mediators of intrinsic apoptosis that permeabilize the mitochondrial outer membrane. BAX activation requires its translocation from cytosol to mitochondria where conformational changes cause its oligomerization. To better understand the critical step of translocation, we examined its blockade by mutation near the C terminus (P168G) or by antibody binding near the N terminus. Similarities in the crystal structures of wild-type and BAX P168G but significant other differences suggest that cytosolic BAX exists as an ensemble of conformers, and that the distribution of conformers within the ensemble determines the different functions of wild-type and mutant proteins. We also describe the structure of BAX in complex with an antibody, 3C10, that inhibits cytosolic BAX by limiting exposure of the membrane-associating helix α9, as does the P168G mutation. Our data for both means of BAX inhibition argue for an allosteric model of BAX regulation that derives from properties of the ensemble of conformers.

PubMed: 30122452
DOI: 10.1016/j.str.2018.07.006

Experimental method

X-RAY DIFFRACTION (1.997 Å)