X-ray crystal structure of human calcium-bound S100A1

Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):215-221. doi: 10.1107/S2053230X17003983. Epub 2017 Mar 22.

Abstract

S100A1 is a member of the S100 family of Ca2+-binding proteins and regulates several cellular processes, including those involved in Ca2+ signaling and cardiac and skeletal muscle function. In Alzheimer's disease, brain S100A1 is overexpressed and gives rise to disease pathologies, making it a potential therapeutic target. The 2.25 Å resolution crystal structure of Ca2+-S100A1 is solved here and is compared with the structures of other S100 proteins, most notably S100B, which is a highly homologous S100-family member that is implicated in the progression of malignant melanoma. The observed structural differences in S100A1 versus S100B provide insights regarding target protein-binding specificity and for targeting these two S100 proteins in human diseases using structure-based drug-design approaches.

Keywords: Alzheimer's disease; S100; S100A1; S100B; calcium-binding proteins; cardiomyopathy; crystal structure.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Calcium / chemistry*
  • Calcium / metabolism
  • Cations, Divalent
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Interaction Domains and Motifs
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Multimerization
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • S100 Calcium Binding Protein beta Subunit / chemistry*
  • S100 Calcium Binding Protein beta Subunit / genetics
  • S100 Calcium Binding Protein beta Subunit / metabolism
  • S100 Proteins / chemistry*
  • S100 Proteins / genetics
  • S100 Proteins / metabolism
  • Sequence Alignment
  • Structural Homology, Protein

Substances

  • Cations, Divalent
  • Protein Isoforms
  • Recombinant Proteins
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • S100A1 protein
  • S100B protein, human
  • Calcium