Work

Metal‐Coordination Specificity and Structural Dynamics of C. elegans Metallothionein I: Insights From 3D Modeling and MD Simulations

Year: 2025

Type: article

Abstract: ABSTRACT Metallothioneins (MTLs) are small, cysteine‐rich proteins known for their ability to bind metal ions and exhibit flexible, disordered structures. The structural and functional characteristics of metallothionein I (MTL‐1) from Caenorhabditis elegans were investigated , focusing on its behavior in both metal free (MTL‐1 Apo) and metal‐bond states with Zn 2+ , Cd 2+ , Cu 2+ , Hg 2+ , and Pb 2+ divalent metal ions. Using molecular dynamics simulations and 3D modeling via AlphaFold, we characterized the flexibility and stability of MTL. The MTL‐1 Apo form displayed high flexibility, aligning with its intrinsically disordered protein (IDP) nature, with 89.3% of its structure composed of coils, bends, and turns. Metal binding significantly enhanced the protein's stability, particularly with Zn 2+ , Cd 2+ , Cu 2+ , and Hg 2+ , reducing root mean square deviation (RMSD), root mean square fluctuation (RMSF), accessible surface area (SASA) and radius of gyration ( R g ) values, indicating structural compaction. Conversely, Pb 2+ showed a weaker stabilizing effect, with a more dynamic and less stable structure. Structural analysis revealed that conserved cysteine residues coordinate the metal through strong thiolate interactions, with additional contributions from non‐cysteine residues, such as Glu and Lys. The study underscores the importance of incorporating intrinsically disordered protein models in MD simulations to provide deeper insights into how metallothionein's flexibility and stability vary in response to different metal ions, offering a structural perspective on their biological interactions and behavior under diverse environmental conditions. While thermodynamic aspects were not directly assessed, the results reveal consistent conformation trends across different metal coordination states.

Source: Proteins Structure Function and Bioinformatics

DOI: 10.1002/prot.70054

Authors: Nilvea Ramalho de Oliveira, Andrei Santos Siqueira, Paulo Sérgio Alves Bueno, Evonnildo Costa Gonçalves, Juliano Zanette

Institutions: Universidade Federal do Rio Grande, Universidade Federal do Rio Grande do Sul, Universidade Federal do Pará, Universidade Estadual de Maringá

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,550

Funders: International Foundation for Science, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Organisation for the Prohibition of Chemical Weapons