Evidence map›Paper›PMID 40679149›Full record

ArticleThe journal of physical chemistry letters2025

Electrostatic Clamp and Loop Dynamics Dictate Caspase-8 Cleavage of the Apoptotic Protein Bid.

Chien-Lun Hung, Wen-Hsien Wang, Yu-Chuan Chang, Yei-Chen Lai, Yun-Wei Chiang

Abstract read
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In one paragraph

Article in The journal of physical chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Chien-Lun HungDepartment of Chemistry, National Tsing Hua University, Hsinchu 300-044, Taiwan.ORCID 0000-0002-2546-1132
Wen-Hsien WangDepartment of Chemistry, National Tsing Hua University, Hsinchu 300-044, Taiwan.
Yu-Chuan ChangDepartment of Chemistry, National Tsing Hua University, Hsinchu 300-044, Taiwan.
Yei-Chen LaiDepartment of Chemistry, National Chung Hsing University, Taichung 402-202, Taiwan.ORCID 0000-0002-5723-5412
Yun-Wei ChiangDepartment of Chemistry, National Tsing Hua University, Hsinchu 300-044, Taiwan.ORCID 0000-0002-2101-8918

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The canonical LQTD motif (residues 56-59) has long been regarded as the sole "address tag" that directs Caspase-8 to cleave the pro-apoptotic protein Bid at D59. Here we overturn this view, showing that Bid's previously uncharted 42-residue "disordered" loop furnishes a second layer of control that can either accelerate or block cleavage. Alanine scanning, MD simulations, DEER spectroscopy, and AlphaFold reveal two physical modules in this loop: an electrostatic clamp formed by E53-D54-E55 that secures the substrate upstream of LQTD, and an entropic flexibility switch at S61-Q62 that modulates catalysis. Phosphorylation at S61 locks the switch and halts proteolysis, whereas a double-alanine substitution (S61A-Q62A) loosens intraloop hydrogen bonding and boosts cleavage by ∼50%. Loop charge, dynamics, and post-translational modification thus cooperate to set Caspase-8 specificity, establishing dynamic loops as tunable physical targets for chemical control of apoptotic signaling.

Indexed as

BH3 Interacting Domain Death Agonist ProteinCaspase 8ApoptosisHumansHydrogen BondingMolecular Dynamics SimulationPhosphorylationProteolysisStatic ElectricityBH3 Interacting Domain Death Agonist ProteinCaspase 8

Identifiers

PMID40679149
PMCPMC12319900

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.