Source 1primary paper2018
Toolkit/human Inward Rectifier K+ Channel Kir2.1
human Inward Rectifier K+ Channel Kir2.1
Also known as: Kir2.1
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Human inward rectifier K+ channel Kir2.1 was used as a protein scaffold to identify engineerable allosteric sites through domain insertion permissibility mapping. Insertion of light-switchable domains into existing or latent allosteric sites, but not other positions, rendered Kir2.1 activity sensitive to light.
Usefulness & Problems
Why this is useful
Kir2.1 is useful as an experimental scaffold for locating positions that can support engineered allosteric control. The reported work indicates that permissive insertion sites can guide the placement of light-switchable domains to create light-responsive ion channel function.
Source:
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Problem solved
This tool addresses the problem of identifying where regulatory domains can be inserted into an ion channel to achieve engineered allosteric control. The cited study establishes domain insertion permissibility in human Kir2.1 as an experimental paradigm for finding such engineerable sites.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Techniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Light
Implementation Constraints
Implementation involved inserting exogenous domains into human Kir2.1 and assessing insertion permissibility as a readout for engineerable allostery. The supplied evidence supports domain insertion of light-switchable modules, but does not specify construct architecture, linker design, expression system, or electrophysiological assay details.
The evidence provided is limited to a single reported study centered on Kir2.1 as a test scaffold. The specific light-switchable domains, optical wavelengths, quantitative channel performance, and validation across broader biological contexts are not described in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Source 2primary paper2012Nature Communications
Ranked Claims
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
Approval Evidence
2 sources8 linked approval claimsfirst-pass slug human-inward-rectifier-k-channel-kir2-1
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Source:
Here we use human Inward Rectifier K+ Channel Kir2.1
Source:
context dependencesupports
Many allosterically regulated sites in Kir2.1 or equivalent sites in homologs show differential permissibility that depends on the structural properties of the inserted domain.
Many allosterically regulated sites in Kir2.1 or sites equivalent to those regulated in homologs, such as G-protein-gated inward rectifier K + channels (GIRK), have differential permissibility; that is, for these sites permissibility depends on the structural properties of the inserted domain.
Source:
experimental paradigmsupports
Domain insertion permissibility is established as a new experimental paradigm to identify engineerable allosteric sites in human Kir2.1.
Here we use human Inward Rectifier K + Channel Kir2.1 to establish domain insertion ‘permissibility’ as a new experimental paradigm to identify engineerable allosteric sites.
Source:
functional engineering resultsupports
Inserting light-switchable domains into existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into either existing or latent allosteric sites, but not elsewhere, renders Kir2.1 activity sensitive to light.
Source:
mechanistic associationsupports
In Kir2.1, domain insertion permissibility is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
Source:
proposed metricsupports
Differential permissibility is proposed as a metric of both existing and latent allostery in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of both existing and latent allostery in Kir2.1.
Source:
allosteric capacity inferencesupports
Differential permissibility is proposed as a metric of latent allosteric capacity in Kir2.1.
Our data and the well-established link between protein dynamics and allostery led us to propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.
Source:
engineered responsivenesssupports
Inserting light-switchable domains into Kir2.1 sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
In support of this notion, inserting light-switchable domains into sites with predicted latent allosteric capacity renders Kir2.1 activity sensitive to light.
Source:
structure function relationshipsupports
In Kir2.1, site-specific permissibility to domain insertion is best explained by dynamic protein properties such as conformational flexibility.
We find that permissibility is best explained by dynamic protein properties, such as conformational flexibility.
Source:
Comparisons
Source-backed strengths
The main strength is that insertion permissibility in Kir2.1 was directly linked to successful engineering of light sensitivity, with functional effects observed when light-switchable domains were inserted into existing or latent allosteric sites but not elsewhere. The evidence also indicates that permissibility can reveal both known and previously latent allosteric positions.
Ranked Citations
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