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Evolutionary-Conserved Allosteric Properties of Three Neuronal Calcium Sensor Proteins
Valerio Marino1,2, Daniele Dell'Orco1
1Section of Biological Chemistry, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy.
Frontiers in Molecular Neuroscience
|March 23, 2019
Summary
Neuronal Calcium Sensors (NCS) use calcium ions to change shape, enabling them to interact with specific targets. This study reveals key amino acids involved in these allosteric communications and their evolutionary conservation.
Area of Science:
- Biochemistry and Molecular Biology
- Neuroscience
- Structural Biology
Background:
- Neuronal Calcium Sensors (NCS) are vital proteins in neuronal signaling, undergoing conformational changes upon calcium binding.
- These changes are critical for target recognition and initiating downstream biological processes.
- Understanding the allosteric communication within NCS is essential for deciphering neuronal function.
Purpose of the Study:
- To comprehensively analyze the allosteric communication between calcium-binding sites and target interfaces in NCS1, recoverin (Rec), and GCAP1.
- To investigate the role of specific amino acids in mediating these interactions and their evolutionary conservation.
- To elucidate the structural dynamics underlying calcium-dependent signaling in neurons.
Main Methods:
- Extensive Molecular Dynamics simulations were used to build Protein Structure Networks (PSNs) for NCS1 and Rec in various calcium-bound states and in complex with target peptides.
- Structural network analysis was employed to identify key residues and map allosteric pathways.
- Comparative analysis with homologous proteins using multiple sequence alignments was performed.
Main Results:
- Allosteric inter-domain interactions between calcium-binding sites and target recognition residues were identified in NCS1.
- Robust long-range allosteric interactions were observed in Rec, particularly originating from the EF3 motif.
- A key residue, Tyr 86 in Rec, was found to be crucial for intra- and inter-molecular communication, independent of calcium or target presence.
Conclusions:
- The study highlights the critical role of specific amino acids in mediating allosteric communication within NCS proteins.
- An evolution-driven correlation between highly interactive amino acids (hubs) and their conservation is proposed, essential for signaling dynamics.
- These findings provide insights into the molecular mechanisms of neuronal calcium signaling and protein evolution.
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