Following activation, the cytoplasmic pattern recognition
receptor nucleotide-binding oligomerization domain-containing
protein 1 (NOD1) interacts with its adaptor protein receptor-
interacting protein 2 (RIP2) to propagate immune signaling
and initiate a proinflammatory immune response. This interaction
is mediated by the caspase recruitment domain (CARD) of
both proteins. Polymorphisms in immune proteins can affect
receptor function and predispose individuals to specific autoinflammatory
disorders. In this report, we show that mutations in
helix 2 of the CARD of NOD1 disrupted receptor function but
did not interfere with RIP2 interaction. In particular, N43S, a
rare polymorphism, resulted in receptor dysfunction despite
retaining normal cellular localization, protein folding, and an ability
to interact with RIP2. Mutation of Asn-43 resulted in an
increased tendency to form dimers, which we propose is the source
of this dysfunction.Wealso demonstrate that mutation of Lys-443
and Tyr-474 in RIP2 disrupted the interaction with NOD1. Mapping
the key residues involved in the interaction between NOD1
and RIP2 to theknownstructures ofCARDcomplexes revealed the
likely involvement of both type I and type III interfaces in the
NOD1RIP2 complex. Overall we demonstrate that the NOD1-
RIP2 signaling axis is more complex than previously assumed, that
simple engagement ofRIP2is insufficient to mediate signaling,and
that the interaction between NOD1 and RIP2 constitutes multiple
CARD-CARD interfaces.
Psst...
Do you want to get language learning tips and resources every week or two? Join our mailing list to receive new ways to improve your language learning in your inbox!
Join the listEnglish Audio Request
|
English
/
Engagement of Nucleotide-binding Oligomerization Domaincontaining Protein 1 (NOD1) by Receptor-interacting Protein 2 (RIP2) Is Insufficient …
209
Words
/
2 Recordings
/
1 Comments
|
Recordings
-
Engagement of Nucleotide-binding Oligomerization Domaincontaining Protein 1 (NOD1) by Receptor-interacting Protein 2 (RIP2) Is Insufficient for Signal Transduction ( recorded by
asianpersuasion3
),
Midwestern
Download
Unlock
Corrected Textmore↓Following activation, the cytoplasmic pattern recognition
receptor nucleotide-binding oligomerization domain-containing
protein 1 (NOD1) interacts with its adaptor protein receptor-
interacting protein 2 (RIP2) to propagate immune signaling
and initiate a proinflammatory immune response. This interaction
is mediated by the caspase recruitment domain (CARD) of
both proteins. Polymorphisms in immune proteins can affect
receptor function and predispose individuals to specific autoinflammatory
disorders. In this report, we show that mutations in
helix 2 of the CARD of NOD1 disrupted receptor function but
did not interfere with RIP2 interaction. In particular, N43S, a
rare polymorphism, resulted in receptor dysfunction despite
retaining normal cellular localization, protein folding, and an ability
to interact with RIP2. Mutation of Asn-43 resulted in an
increased tendency to form dimers, which we propose is the source
of this dysfunction. We also demonstrate that mutation of Lys-443
and Tyr-474 in RIP2 disrupted the interaction with NOD1. Mapping
the key residues involved in the interaction between NOD1
and RIP2 to the known structures of CARD complexes revealed the
likely involvement of both type I and type III interfaces in the
NOD1 RIP2 complex. Overall, we demonstrate that the NOD1-
RIP2 signaling axis is more complex than previously assumed, that
simple engagement of RIP2 is insufficient to mediate signaling, and
that the interaction between NOD1 and RIP2 constitutes multiple
CARD-CARD interfaces. -
Engagement of Nucleotide-binding Oligomerization Domaincontaining Protein 1 (NOD1) by Receptor-interacting Protein 2 (RIP2) Is Insufficient for Signal Transduction ( recorded by
asianpersuasion3
),
Midwestern
Download
Unlock
Corrected Textmore↓Following activation, the cytoplasmic pattern recognition
receptor nucleotide-binding oligomerization domain-containing
protein 1 (NOD1) interacts with its adaptor protein receptor-
interacting protein 2 (RIP2) to propagate immune signaling
and initiate a proinflammatory immune response. This interaction
is mediated by the caspase recruitment domain (CARD) of
both proteins. Polymorphisms in immune proteins can affect
receptor function and predispose individuals to specific autoinflammatory
disorders. In this report, we show that mutations in
helix 2 of the CARD of NOD1 disrupted receptor function but
did not interfere with RIP2 interaction. In particular, N43S, a
rare polymorphism, resulted in receptor dysfunction despite
retaining normal cellular localization, protein folding, and an ability
to interact with RIP2. Mutation of Asn-43 resulted in an
increased tendency to form dimers, which we propose is the source
of this dysfunction. We also demonstrate that mutation of Lys-443
and Tyr-474 in RIP2 disrupted the interaction with NOD1. Mapping
the key residues involved in the interaction between NOD1
and RIP2 to the known structures of CARD complexes revealed the
likely involvement of both type I and type III interfaces in the
NOD1 RIP2 complex. Overall, we demonstrate that the NOD1-
RIP2 signaling axis is more complex than previously assumed, that
simple engagement of RIP2 is insufficient to mediate signaling, and
that the interaction between NOD1 and RIP2 constitutes multiple
CARD-CARD interfaces.
Comments
You can use our built-in RhinoRecorder to record from within your browser, or you may also use the form to upload an audio file for this Audio Request.
Don't have audio recording software? We recommend Audacity. It's free and easy to use.
I hope I could help. I had no idea what I was reading, and some of the vocabulary was very technical, so I may have mispronounced some of the words, particularly caspase haha.