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Structural Modeling and Dynamics of the Full-Length Homer1 Multimer.
Zsófia E Kálmán1, András Czajlik2, Brigitta Maruzs1
1Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary.
Proteins
|November 21, 2025
Summary
Homer proteins are key to brain cell communication. This study reveals new insights into Homer1 protein flexibility, suggesting it plays a dynamic role in postsynaptic network organization.
Area of Science:
- Neuroscience
- Molecular Biology
- Structural Biology
Background:
- Homer proteins act as crucial scaffolds in the postsynaptic density, organizing neurotransmitter receptor complexes.
- Full-length Homer1 forms a homotetramer, interacting with target proteins via its EVH1 domain and coiled-coil region.
Purpose of the Study:
- To determine the atomistic structure and dynamics of the Homer1 coiled coil and EVH1 domains.
- To understand how these structural features influence the overall Homer1 tetramer organization and flexibility.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy for EVH1 domain structure and dynamics.
- Atomistic modeling and molecular dynamics simulations for the coiled coil region.
Main Results:
- NMR ensemble of the EVH1 domain shows subtle differences, indicating potential ligand-induced conformational changes.
- Molecular dynamics reveal distinct flexibility patterns in the coiled coil, with the N-terminal segment showing significant motion.
- The N-terminal coiled coil's high conservation suggests functional importance of its dynamics.
Conclusions:
- The Homer1 tetramer exhibits previously uncharacterized flexibility, particularly in its coiled coil region.
- This flexibility may facilitate dynamic rearrangements within the postsynaptic protein network.
- These findings offer new perspectives on Homer1's role in synaptic plasticity and function.
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