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Computer-aided molecular modeling and structural analysis of the human centromere protein-HIKM complex
  • Olanrewaju Durojaye
Olanrewaju Durojaye
University of Science and Technology of China
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Abstract

Protein-peptide and protein-protein interactions play an essential role in different functional and structural cellular organizational aspects. While X-ray crystallography generates 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. 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 leads 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 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. Results from this study substantiates the existing hypothesis that the human CENP-HIK complex share a similar architecture with its fungal and yeast orthologs, and likewise validates the binding mode of CENP-M to the C-terminus of the human CENP-I based on existing experimental reports.