6BF2

Solution structure of a Bcl-xL S62E mutant

Replaces:  5L1Y

Summary for 6BF2

• Entry DOI: 10.2210/pdb6bf2/pdb
• NMR Information: BMRB: 30150
• Descriptor: Bcl-2-like protein 1 (1 entity in total)
• Functional Keywords: apoptosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 23711.98

Authors

Viacava Follis, A.,Phillips, A.,Kriwacki, R.W. (deposition date: 2017-10-25, release date: 2017-11-08, Last modification date: 2024-05-15)

Primary citation

Follis, A.V.,Llambi, F.,Kalkavan, H.,Yao, Y.,Phillips, A.H.,Park, C.G.,Marassi, F.M.,Green, D.R.,Kriwacki, R.W.
Regulation of apoptosis by an intrinsically disordered region of Bcl-xL.
Nat. Chem. Biol., 14:458-465, 2018

PubMed Abstract: Intrinsically disordered regions (IDRs) of proteins often regulate function upon post-translational modification (PTM) through interactions with folded domains. An IDR linking two α-helices (α1-α2) of the antiapoptotic protein Bcl-xL experiences several PTMs that reduce antiapoptotic activity. Here, we report that PTMs within the α1-α2 IDR promote its interaction with the folded core of Bcl-xL that inhibits the proapoptotic activity of two types of regulatory targets, BH3-only proteins and p53. This autoregulation utilizes an allosteric pathway whereby, in one direction, the IDR induces a direct displacement of p53 from Bcl-xL coupled to allosteric displacement of simultaneously bound BH3-only partners. This pathway operates in the opposite direction when the BH3-only protein PUMA binds to the BH3 binding groove of Bcl-xL, directly displacing other bound BH3-only proteins, and allosterically remodels the distal site, displacing p53. Our findings show how an IDR enhances functional versatility through PTM-dependent allosteric regulation of a folded protein domain.

PubMed: 29507390
DOI: 10.1038/s41589-018-0011-x

Experimental method

SOLUTION NMR