2IMT

The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site

Summary for 2IMT

• Entry DOI: 10.2210/pdb2imt/pdb
• Related: 1BXL 1F16 1LXL 1MAZ 1MK3 1WSX 2IMS
• Descriptor: Apoptosis regulator BAK, ZINC ION (3 entities in total)
• Functional Keywords: dimer, apoptosis
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion membrane ; Single-pass membrane protein : Q16611
• Total number of polymer chains: 1
• Total formula weight: 19241.88

Authors

Moldoveanu, T.,Liu, Q.,Tocilj, A.,Watson, M.,Shore, G.C.,Gehring, K.B. (deposition date: 2006-10-04, release date: 2007-01-23, Last modification date: 2023-08-30)

Primary citation

Moldoveanu, T.,Liu, Q.,Tocilj, A.,Watson, M.,Shore, G.,Gehring, K.
The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site.
Mol.Cell, 24:677-688, 2006

PubMed Abstract: BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP) drives cell death during development and tissue homeostasis from zebrafish to humans. In most cancers, this pathway is inhibited by BCL-2 family antiapoptotic members, which bind and block the action of proapoptotic BCL proteins. We report the 1.5 A crystal structure of calpain-proteolysed BAK, cBAK, to reveal a zinc binding site that regulates its activity via homodimerization. cBAK contains an occluded BH3 peptide binding pocket that binds a BID BH3 peptide only weakly . Nonetheless, cBAK requires activation by truncated BID to induce cytochrome c release in mitochondria isolated from bak/bax double-knockout mouse embryonic fibroblasts. The BAK-mediated MOMP is inhibited by low micromolar zinc levels. This inhibition is alleviated by mutation of the zinc-coordination site in BAK. Our results link directly the antiapoptotic effects of zinc to BAK.

PubMed: 17157251
DOI: 10.1016/j.molcel.2006.10.014

Experimental method

X-RAY DIFFRACTION (1.49 Å)