A structural code for assembly specificity in GID/CTLH-type E3 ligases
Pia Maria van Gen Hassend1, Hermann Schindelin1
1Institute of Structural Biology, Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Elife
|April 8, 2026
Summary
Scientists decoded the assembly specificity code for GID/CTLH-type E3 ligases, revealing how conserved features dictate subunit arrangement in these ring-shaped protein complexes.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- GID/CTLH-type E3 ligases form conserved ring-shaped structures from repeating modules.
- The molecular rules governing specific subunit arrangement within these ligases were previously unknown.
Purpose of the Study:
- To decode the structural 'assembly specificity code' responsible for CRA-CRA pairing in GID/CTLH-type E3 ligases.
- To understand the molecular basis of high-affinity interactions and subunit selectivity.
Main Methods:
- Crystal structures of multiple CTLH-CRA domains were determined.
- Quantitative binding analyses were performed.
- Targeted perturbations of conserved sequence and geometric features were utilized.
Main Results:
- Several interfaces exhibit exceptionally high affinity, reaching the picomolar range.
- Conserved sequence and geometric features ensure specific pairing between cognate subunits.
- Perturbing these features reprogrammed pairing preferences, allowing non-native interactions.
Conclusions:
- The study reveals the molecular logic preserving the architecture of GID/CTLH-type E3 ligases.
- The assembly code is decipherable and engineerable, offering a foundation for reconfiguring these E3 ligases.
Related Concept Videos
01:30Assembly of Signaling Complexes
7.2K
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,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
7.2K
01:57Protein Complexes with Interchangeable Parts
3.1K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.1K
01:25Structure of Cadherins
5.2K
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...
5.2K
01:29Cytoskeletal Proteins in Bacteria
4.5K
Bacterial cells were initially considered simple, randomly organized structures lacking a cytoskeleton. However, the discovery of cytoskeleton homologs in bacteria led to the change of this opinion. Bacterial cytoskeletal filaments regulate the cell shape, cell polarity, cell division, and partitioning of plasmids during cell division. It was later discovered that bacterial cytoskeletal proteins, mainly actin and tubulin homologs, are diverse compared to their eukaryotic counterparts. On the...
4.5K
01:14Generation of Straight or Branched Actin Filaments
4.0K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
4.0K
00:49Ligand Binding and Linkage
6.0K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
6.0K