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Conformational Dynamics and Molecular Characterization of Alsin MORN monomer and dimeric assemblies
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  • Marcello Miceli,
  • Marco Cannariato,
  • Riccardo Tortarolo,
  • Lorenzo Pallante,
  • Eric A. Zizzi,
  • Marco A. Deriu
Marcello Miceli
Politecnico di Torino Dipartimento di Ingegneria Meccanica e Aerospaziale
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Marco Cannariato
Politecnico di Torino Dipartimento di Ingegneria Meccanica e Aerospaziale
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Riccardo Tortarolo
Politecnico di Torino Dipartimento di Ingegneria Meccanica e Aerospaziale
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Lorenzo Pallante
Politecnico di Torino Dipartimento di Ingegneria Meccanica e Aerospaziale
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Eric A. Zizzi
Politecnico di Torino Dipartimento di Ingegneria Meccanica e Aerospaziale
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Marco A. Deriu
Politecnico di Torino Dipartimento di Ingegneria Meccanica e Aerospaziale

Corresponding Author:[email protected]

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Abstract

Despite the ubiquity of Membrane Occupation Recognition Nexus (MORN) motifs across diverse species in both eukaryotic and prokaryotic organisms, these protein domains remain poorly characterized. Their significance is underscored in the context of the Alsin protein, implicated in the debilitating condition known as Infantile-onset Ascending Hereditary Spastic Paralysis (IAHSP). Studies have proposed that mutations within the Alsin MORN domain disrupt proper protein assembly, precluding the formation of the requisite tetrameric configuration essential for the protein’s inherent biological activity. However, a comprehensive understanding of the relationship between the biological functions of Alsin and its three-dimensional molecular structure is hindered by the lack of available experimental structures. In this study, by comparing experimentally resolved MORN domains, we predicted a three-dimensional structure for the putative MORN of Alsin. Furthermore, inspired by experimental pieces of evidence from previous studies, we employed the developed models to predict and investigate two homo-dimeric assemblies, characterising their stability. This study’s insights into the three-dimensional structure of the Alsin MORN domain and the stability dynamics of its homo-dimeric assemblies suggest an antiparallel linear configuration stabilized by a non-covalent interaction network. The elucidation of these intricate molecular relationships holds promise for advancing our understanding of pathogenic mechanisms and facilitating the development of treatments for this severe neurodegenerative disorder.
Submitted to PROTEINS: Structure, Function, and Bioinformatics
28 Feb 2024Review(s) Completed, Editorial Evaluation Pending
05 Jun 20241st Revision Received
06 Jun 2024Submission Checks Completed
06 Jun 2024Assigned to Editor
27 Jun 2024Editorial Decision: Accept