Overall conformation of covalently stabilized domain-swapped dimer of human cystatin C in solution

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Human cystatin C (HCC), a small protein, plays a crucial role in inhibition of cysteine proteases. The most common structural form of human cystatin C in crystals is a dimer, which has been evidenced both for the native protein and its mutants. In these structures, HCC dimers were formed through the mechanism of domain swapping. The structure of the monomeric form of human cystatin C was determined for V57N mutant and the mutant with the engineered disulfide bond (L47C)–(G69C) (known as stab1-HCC). On the basis of stab1-HCC, a number of covalently stabilized oligomers, including also dimers have been obtained. The aim of this study was to analyze the structure of the covalently stabilized dimer HCC in solution by the small angle X-ray scattering (SAXS) technique and synchrotron radiation. Experimental data confirmed that in solution this protein forms a dimer, which is characterized by the radius of gyration RG = 3.1 nm and maximum intramolecular distance Dmax = 10.3 nm. Using the ab initio method and program DAMMIN, we propose a low resolution structure of stabilized covalently cystatin C in solution. Stab-HCC dimer adopts in solution an elongated conformation, which is well reconstructed by the ab initio model.

Detaljer

Författare
Externa organisationer
  • Adam Mickiewicz University in Poznań
  • University of Gdansk
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Strukturbiologi
  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)136-140
Antal sidor5
TidskriftNuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms
Volym411
StatusPublished - 2017 nov 15
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa