4U2U

Bak domain swapped dimer induced by BidBH3 with CHAPS

Summary for 4U2U

• Entry DOI: 10.2210/pdb4u2u/pdb
• Related: 4U2V
• Descriptor: Bcl-2 homologous antagonist/killer (2 entities in total)
• Functional Keywords: apoptosis, bak, bcl-2
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 37960.54

Authors

Brouwer, J.M.,Colman, P.M.,Czabotar, P.E. (deposition date: 2014-07-18, release date: 2014-09-10, Last modification date: 2023-09-27)

Primary citation

Brouwer, J.M.,Westphal, D.,Dewson, G.,Robin, A.Y.,Uren, R.T.,Bartolo, R.,Thompson, G.V.,Colman, P.M.,Kluck, R.M.,Czabotar, P.E.
Bak Core and Latch Domains Separate during Activation, and Freed Core Domains Form Symmetric Homodimers.
Mol.Cell, 55:938-946, 2014

PubMed Abstract: Apoptotic stimuli activate and oligomerize the proapoptotic proteins Bak and Bax, resulting in mitochondrial outer-membrane permeabilization and subsequent cell death. This activation can occur when certain BH3-only proteins interact directly with Bak and Bax. Recently published crystal structures reveal that Bax separates into core and latch domains in response to BH3 peptides. The distinguishing characteristics of BH3 peptides capable of directly activating Bax were also elucidated. Here we identify specific BH3 peptides capable of "unlatching" Bak and describe structural insights into Bak activation and oligomerization. Crystal structures and crosslinking experiments demonstrate that Bak undergoes a conformational change similar to that of Bax upon activation. A structure of the Bak core domain dimer provides a high-resolution image of this key intermediate in the pore-forming oligomer. Our results confirm an analogous mechanism for activation and dimerization of Bak and Bax in response to certain BH3 peptides.

PubMed: 25175025
DOI: 10.1016/j.molcel.2014.07.016

Experimental method

X-RAY DIFFRACTION (2.9 Å)