Interaction of serum amyloid A with human cystatin Cuidentification of binding sites

Research output: Contribution to journalArticle

Abstract

Serum amyloid A (SAA) is a multifunctional acute-phase protein whose natural role seems to be participation in many physiologic and pathological processes. Prolonged increased SAA level in a number of chronic inflammatory and neoplastic diseases gives rise to reactive systemic amyloid A amyloidosis, where the N-terminal 76-amino acid residue-long segment of SAA is deposited as amyloid fibrils. Recently, a specific interaction between SAA and the ubiquitous inhibitor of cysteine proteaseshuman cystatin C (hCC)has been described. Here, we report further evidence corroborating this interaction, and the identification of the SAA and hCC binding sites in the SAAhCC complex, using a combination of selective proteolytic excision and high-resolution mass spectrometry. The shortest binding site in the SAA sequence was determined as SAA(86104), whereas the binding site in hCC sequence was identified as hCC(96102). Binding specificities of both interacting sequences were ascertained by affinity experiments (ELISA) and by registration of mass spectrum of SAAhCC complex. Copyright (c) 2012 John Wiley & Sons, Ltd.

Details

Authors
  • Marta Spodzieja
  • Aneta Szymanska
  • Aleksandra Kolodziejczyk
  • Martyna Pradzinska
  • Martyna Maszota
  • Piotr Stefanowicz
  • Zbigniew Szewczuk
  • Anders Grubb
  • Paulina Czaplewska
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology
  • Medicinal Chemistry

Keywords

  • serum amyloid A, human cystatin C, protein-protein interaction, mass, spectrometry
Original languageEnglish
Pages (from-to)513-524
JournalJournal of Molecular Recognition
Volume25
Issue number10
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes