Crystal structure of human Cep57 C-terminal domain reveals the presence of leucine zipper and the potential microtubule binding region

Proteins. 2024 Sep;92(9):1137-1143. doi: 10.1002/prot.26698. Epub 2024 May 3.

Abstract

Cep57, a vital centrosome-associated protein, recruits essential regulatory enzymes for centriole duplication. Its dysfunction leads to anomalies, including reduced centrioles and mosaic-variegated aneuploidy syndrome. Despite functional investigations, understanding structural aspects and their correlation with functions is partial till date. We present the structure of human Cep57 C-terminal microtubule binding (MT-BD) domain, revealing conserved motifs ensuring functional preservation across evolution. A leucine zipper, with an adjacent possible microtubule-binding region, potentially forms a stabilizing scaffold for microtubule nucleation-accommodating pulling and tension from growing microtubules. This study highlights conserved structural features of Cep57 protein, compares them with other analogous proteins, and explores how protein function is maintained across diverse organisms.

Keywords: coiled‐coil; evolution; leucine zipper; microtubule‐binding; structure.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Cycle Proteins* / chemistry
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Crystallography, X-Ray
  • Humans
  • Leucine Zippers*
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules* / chemistry
  • Microtubules* / metabolism
  • Models, Molecular
  • Nuclear Proteins
  • Protein Binding*
  • Protein Domains

Substances

  • CEP57 protein, human
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins