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Computer-aided molecular modeling and structural analysis of the human centromere protein–HIKM complex

Background Protein–peptide and protein–protein interactions play an essential role in different functional and structural cellular organizational aspects. While Cryo-EM and X-ray crystallography generate the most complete structural characterization, most biological interactions exist in biomolecula...

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Published in:Beni-Suef University journal of basic and applied sciences 2022-12, Vol.11 (1), p.1-18, Article 101
Main Authors: Uzoeto, Henrietta Onyinye, Cosmas, Samuel, Ajima, Judith Nnedimkpa, Arazu, Amarachukwu Vivian, Didiugwu, Chizoba Maryann, Ekpo, Daniel Emmanuel, Ibiang, Glory Omini, Durojaye, Olanrewaju Ayodeji
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Language:English
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Summary:Background Protein–peptide and protein–protein interactions play an essential role in different functional and structural cellular organizational aspects. While Cryo-EM and X-ray crystallography generate the most complete structural characterization, most biological interactions exist in biomolecular complexes that are neither compliant nor responsive to direct experimental analysis. The development of computational docking approaches is therefore necessary. This starts from component protein structures to the prediction of their complexes, preferentially with precision close to complex structures generated by X-ray crystallography. Results To guarantee faithful chromosomal segregation, there must be a proper assembling of the kinetochore (a protein complex with multiple subunits) at the centromere during the process of cell division. As an important member of the inner kinetochore, defects in any of the subunits making up the CENP-HIKM complex lead to kinetochore dysfunction and an eventual chromosomal mis-segregation and cell death. Previous studies in an attempt to understand the assembly and mechanism devised by the CENP-HIKM in promoting the functionality of the kinetochore have reconstituted the protein complex from different organisms including fungi and yeast. Here, we present a detailed computational model of the physical interactions that exist between each component of the human CENP-HIKM, while validating each modeled structure using orthologs with existing crystal structures from the protein data bank. Conclusions Results from this study substantiate the existing hypothesis that the human CENP-HIK complex shares a similar architecture with its fungal and yeast orthologs, and likewise validate the binding mode of CENP-M to the C-terminus of the human CENP-I based on existing experimental reports. Graphical abstract
ISSN:2314-8543
2314-8543
DOI:10.1186/s43088-022-00285-1