Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Checking the conformational stability of cystatin C and its L68Q variant by molecular dynamics studies: Why is the L68Q variant amyloidogenic?

In English

Författare

  • S Rodziewicz-Motowidlo
  • Maria Wahlbom
  • Xin Wang
  • J Lagiewka
  • R Janowski
  • M Jaskolski
  • Anders Grubb
  • Z Grzonka

Summary, in English

Human L68Q cystatin C is one of the known human amyloidogenic proteins. In its native state it is a monomer with alpha/beta structure. Experimental evidence suggests that L68Q variant associates into dimeric intermediates and that the dimers subsequently self-assemble to form amyloid deposits and insoluble fibrils. Details of the pathway of L68Q mutant amyloid formation are unclear; however, different experimental approaches with resolutions at molecular level have provided Some clues. Probably, the stability and flexibility of monomeric L68Q variant play essential roles in the early steps of amyloid formation; thus, it is necessary to characterize early conformational changes of L68Q cystatin C monomers. In this paper, we demonstrate the possibility that the differences between the monomeric forms of wild-type (wt) cystatin C and its L68Q variant are responsible for higher tendency of the L68Q cystatin C amyloidogenesis. We started our studies with the simulations of wt and L68Q cystatin C monomers. Nanosecond time scale molecular dynamics simulations at 308 K were performed using AMBER7.0 program, The results show that the structure of the L68Q monomer was changed, relative to the wt cystatin C structure. The results support earlier speculation that the L68Q point mutation would easily lead to dimer formation. (c) 2006 Published by Elsevier Inc.

Publiceringsår

2006

Språk

Engelska

Sidor

68-78

Publikation/Tidskrift/Serie

Journal of Structural Biology

Volym

154

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Medicinal Chemistry
  • Pharmacology and Toxicology

Nyckelord

  • single-point mutation
  • amyloidosis
  • conformational change
  • human cystatin C
  • molecular dynamics simulation

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1095-8657