2M5B

The NMR structure of the BID-BAK complex

Summary for 2M5B

• Entry DOI: 10.2210/pdb2m5b/pdb
• Related: 2BID 2IMT
• NMR Information: BMRB: 19045
• Descriptor: Bcl-2 homologous antagonist/killer, human_BID_BH3_SAHB (2 entities in total)
• Functional Keywords: bcl-2 family effector bak, bh3-only protein bid, effector direct activation, nmr solution structure of bid-bak complex, mitochondrial outer membrane premeabilization, apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion membrane; Single-pass membrane protein (Potential): Q16611
• Total number of polymer chains: 2
• Total formula weight: 21483.20

Authors

Moldoveanu, T.,Grace, C.R.,Kriwacki, R.W.,Green, D.R. (deposition date: 2013-02-19, release date: 2013-04-17, Last modification date: 2024-10-09)

Primary citation

Moldoveanu, T.,Grace, C.R.,Llambi, F.,Nourse, A.,Fitzgerald, P.,Gehring, K.,Kriwacki, R.W.,Green, D.R.
BID-induced structural changes in BAK promote apoptosis.
Nat.Struct.Mol.Biol., 20:589-597, 2013

PubMed Abstract: The BCL-2-family protein BAK is responsible for mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis. The BCL-2 homology 3 (BH3)-only protein BID activates BAK to perform this function. We report the NMR solution structure of the human BID BH3-BAK complex, which identified the activation site at the canonical BH3-binding groove of BAK. Mutating the BAK BH1 in the groove prevented activation and MOMP but not the binding of BID. BAK BH3 mutations allowed BID binding and activation but blunted function by blocking BAK oligomerization. BAK activation follows a 'hit-and-run' mechanism whereby BID dissociates from the trigger site, which allows BAK oligomerization at an overlapping interface. In contrast, the BH3-only proteins NOXA and BAD are predicted to clash with the trigger site and are not activators of BAK. These findings provide insights into the early stages of BAK activation.

PubMed: 23604079
DOI: 10.1038/nsmb.2563

Experimental method

SOLUTION NMR