Source 1primary paper2020
Toolkit/TRIM21-nanobody chimeras
TRIM21-nanobody chimeras
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
TRIM21-nanobody chimeras are engineered Trim-Away constructs that fuse TRIM21 activity to nanobody-based target recognition. In the cited 2020 work, these chimeras were described as highly active and were further adapted for optogenetic control of targeted protein degradation.
Usefulness & Problems
Why this is useful
These constructs expand the Trim-Away toolbox by coupling TRIM21-mediated degradation to nanobody-directed substrate recognition. The same study indicates that they can be placed under optogenetic control, supporting temporally controlled degradation applications.
Source:
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Source:
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Problem solved
They address the problem of directing TRIM21 ubiquitination activity toward chosen protein targets without relying solely on conventional antibody delivery formats. The cited work also positions them as a way to control targeted degradation with light, although detailed operating parameters are not provided in the supplied evidence.
Source:
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Problem links
Need conditional protein clearance
DerivedTRIM21-nanobody chimeras are engineered Trim-Away constructs that fuse TRIM21 activity to nanobody-based target recognition. In the cited 2020 work, these chimeras were described as highly active and were further adapted for optogenetic control of targeted protein degradation.
Need precise spatiotemporal control with light input
DerivedTRIM21-nanobody chimeras are engineered Trim-Away constructs that fuse TRIM21 activity to nanobody-based target recognition. In the cited 2020 work, these chimeras were described as highly active and were further adapted for optogenetic control of targeted protein degradation.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
activation of trim21 ubiquitination activityDegradationintermolecular dimerization of the trim21 ring domainoptogenetic controlsubstrate-induced clusteringtargeted protein degradationTechniques
No technique tags yet.
Target processes
degradationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: regulator
The construct pattern is supported by domain fusion between TRIM21 and a nanobody, with optional optogenetic control modules mentioned in the source text. Beyond that, the evidence does not provide construct architecture, expression system, cofactor requirements, or delivery details.
The supplied evidence does not specify the nanobody targets, degradation kinetics, light wavelengths, dynamic range, or cellular contexts tested for the chimeras. Independent replication is not provided in the evidence set, and optogenetic implementation details are not described.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.
Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Approval Evidence
1 source2 linked approval claimsfirst-pass slug trim21-nanobody-chimeras
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Source:
general mechanistic implicationsupports
This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.
This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Source:
tool expansionsupports
The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.
We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Source:
Comparisons
Source-backed strengths
The source explicitly describes the TRIM21-nanobody chimeras as highly active. Their design is grounded in a defined TRIM21 activation mechanism in which substrate-induced clustering promotes intermolecular RING-domain dimerization and activates TRIM21 ubiquitination activity.
Compared with GFP-CRY2
TRIM21-nanobody chimeras and GFP-CRY2 address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: light
Compared with lyso-ArchT
TRIM21-nanobody chimeras and lyso-ArchT address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: light
Compared with lyso-ChR2
TRIM21-nanobody chimeras and lyso-ChR2 address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: light
Ranked Citations
- 1.