Related Experiment Video

Updated: Jun 13, 2026

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
10:05

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation

Chao Zheng1, Venkataraman Kabaleeswaran, Yaya Wang

  • 1Weill Medical College, Cornell University, New York, NY 10021, USA.

Molecular Cell
|April 14, 2010
PubMed

Insights

Tumor necrosis factor receptor-associated factors (TRAFs) and inhibitors of apoptosis proteins (IAPs) are key in NF-kappaB signaling. This study reveals how TRAF1 and TRAF2 interact with cIAP2, uncovering TRAF1's role in modulating these interactions.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Immunology

Background:

  • Tumor necrosis factor receptor-associated factors (TRAF1, TRAF2) and inhibitor of apoptosis proteins (cIAP1, cIAP2) are crucial for NF-kappaB signaling pathways.
  • Understanding their interactions is vital for deciphering cellular signaling and immune responses.

Purpose of the Study:

  • To elucidate the structural basis of TRAF-IAP interactions.
  • To investigate the role of TRAF1 in modulating TRAF2:cIAP2 complex formation and function.

Main Methods:

  • X-ray crystallography to determine the structures of TRAF2:cIAP2 and TRAF1:TRAF2:cIAP2 complexes.
  • Mutagenesis studies to confirm key residues at protein-protein interaction interfaces.

Main Results:

  • TRAF2 forms a trimer that interacts with cIAP2.
  • TRAF1 preferentially forms a TRAF1:(TRAF2)2 heterotrimer, which binds cIAP2 more effectively than TRAF2 alone.
  • TRAF1, alongside TRAF2, mediates the interaction in the ternary complex, suggesting a regulatory role.

Conclusions:

  • The crystal structures provide detailed insights into TRAF-IAP complex formation.
  • TRAF1 plays a significant role in modulating TRAF2 interactions with cIAP1/2, impacting TNF signaling regulation.

More Related Videos

Tandem Affinity Purification of Protein Complexes from Eukaryotic Cells11:30

Tandem Affinity Purification of Protein Complexes from Eukaryotic Cells

Published on: January 26, 2017

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.