Evidence map›Paper›PMID 34432240›Full record

ArticleMethods in molecular biology (Clifton, N.J.)2021

Mechanistic and Structural Features of PROTAC Ternary Complexes.

Ryan Casement, Adam Bond, Conner Craigon, Alessio Ciulli

Abstract read
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In one paragraph

Article in Methods in molecular biology (Clifton, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

44 citing papers in PubMed.

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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

4 authors.

Ryan Casement *Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Adam Bond *Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Conner Craigon *Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Alessio CiulliDivision of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Scotland, UK. a.ciulli@dundee.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/M010996/1Medical Research Council MR/N0123735/1
6 · The paper itself

Abstract

The rapid and ever-growing advancements from within the field of proteolysis-targeting chimeras (PROTAC)-induced protein degradation have driven considerable development to gain a deeper understanding of their mode of action. The ternary complex formed by PROTACs with their target protein and E3 ubiquitin ligase is the key species in their substoichiometric catalytic mechanism. Here, we describe the theoretical framework that underpins ternary complexes, including a current understanding of the three-component binding model, cooperativity, hook effect and structural considerations. We discuss in detail the biophysical methods used to interrogate ternary complex formation in vitro, including X-ray crystallography, AlphaLISA, FRET, FP, ITC and SPR. Finally, we provide detailed ITC methods and discuss approaches to assess binary and ternary target engagement, target ubiquitination and degradation that can be used to obtain a more holistic understanding of the mode of action within a cellular environment.

Indexed as

ProteolysisUbiquitin-Protein LigasesUbiquitinationUbiquitin-Protein LigasesBiophysical methods, crystal structuresCooperativityE3 ubiquitin ligaseHook effectProtein ubiquitinationproteolysis-targeting chimeras (PROTACs)Targeted protein degradation (TPD)Target engagementTernary complex

Identifiers

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.