Pro-survival proteins in the B-cell lymphoma-2 (Bcl-2) family have a defined specificity profile for their cell death-inducing BH3-only antagonists. Solution structures of myeloid cell leukaemia-1 (Mcl-1) in complex with the BH3 domains from Noxa and Puma, two proteins regulated by the tumour suppressor p53, show that they bind as amphipathic alpha-helices in the same hydrophobic groove of Mcl-1, using conserved residues for binding. Thermodynamic parameters for the interaction of Noxa, Puma and the related BH3 domains of Bmf, Bim, Bid and Bak with Mcl-1 were determined by calorimetry. These unstructured BH3 domains bind Mcl-1 with affinities that span 3 orders of magnitude, and binding is an enthalpically driven and entropy-enthalpy-compensated process. Alanine scanning analysis of Noxa demonstrated that only a subset of residues is required for interaction with Mcl-1, and these residues are localised to a short highly conserved sequence motif that defines the BH3 domain. Chemical shift mapping of Mcl-1:BH3 complexes showed that Mcl-1 engages all BH3 ligands in a similar way and that, in addition to changes in the immediate vicinity of the binding site, small molecule-wide structural adjustments accommodate ligand binding. Our studies show that unstructured peptides, such as the BH3 domains, behave like their structured counterparts and can bind tightly and selectively in an enthalpically driven process.
Pharmacology, Toxicology and Pharmaceutical Science
3
2%
Immunology and Microbiology
2
1%
Other
8
5%
Unknown
40
25%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 March 2026.
All research outputs
#4,699,124
of 31,591,940 outputs
Outputs from Journal of Molecular Biology
#1,474
of 13,200 outputs
Outputs of similar age
#15,602
of 125,229 outputs
Outputs of similar age from Journal of Molecular Biology
#10
of 99 outputs
Altmetric has tracked 31,591,940 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,200 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.9. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 125,229 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 99 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.
