Dissecting physical structure of calreticulin, an intrinsically disordered Ca 2+-buffering chaperone from endoplasmic reticulum

J Biomol Struct Dyn. 2018 May;36(6):1617-1636. doi: 10.1080/07391102.2017.1330224. Epub 2017 May 26.

Abstract

Calreticulin (CALR) is a Ca2+ binding multifunctional protein that mostly resides in the endoplasmic reticulum (ER) and plays a number of important roles in various physiological and pathological processes. Although the major functions ascribed to CALR are controlling the Ca2+ homeostasis in ER and acting as a lectin-like ER chaperon for many glycoproteins, this moonlighting protein can be found in various cellular compartments where it has many non-ER functions. To shed more light on the mechanisms underlying polyfunctionality of this moonlighting protein that can be found in different cellular compartments and that possesses a wide spectrum of unrelated biological activities, being able to interact with Ca2+ (and potentially other metal ions), RNA, oligosaccharides, and numerous proteins, we used a set of experimental and computational tools to evaluate the intrinsic disorder status of CALR and the role of calcium binding on structural properties and conformational stability of the full-length CALR and its isolated P- and C-domains.

Keywords: calreticulin; chaperone; intrinsically disordered protein; moonlighting protein; posttranslational modifications; protein–protein interaction.

MeSH terms

  • Calcium / chemistry*
  • Calcium-Binding Proteins / chemistry*
  • Calreticulin / chemistry*
  • Endoplasmic Reticulum / chemistry*
  • Escherichia coli / chemistry
  • Humans
  • Lectins / chemistry
  • Molecular Chaperones / chemistry*
  • Oligosaccharides / chemistry
  • Proteins / chemistry
  • RNA / chemistry

Substances

  • Calcium-Binding Proteins
  • Calreticulin
  • Lectins
  • Molecular Chaperones
  • Oligosaccharides
  • Proteins
  • RNA
  • Calcium