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.

The coupling between disulphide status, metallation and dimer interface strength in Cu/Zn superoxide dismutase

In English

Författare

  • Andreas Hornberg
  • Derek Logan
  • Stefan L. Marklund
  • Mikael Oliveberg

Summary, in English

The gain of neurotoxic function in amyotrophic lateral sclerosis (ALS) has been linked to misfolding of the homodimeric enzyme Cu/Zn superoxide dismutase (SOD). Here, we present the crystal structure of fully cysteine-depleted human SOD (SOD (CallA)), representing a reduced, marginally stable intermediate on the folding pathway in vivo that has also been implicated as neurotoxic precursor state. A hallmark of this species is that it fails to dimerise and becomes trapped as a monomer in the absence of the active-site metals. The crystallographic data show that removal of the C57-C146 disulphide bond sets free the interface loop IV in the apo protein, whereas the same loop remains unaffected in the holo protein. Thus, the low dimerisation propensity of disulphide-reduced apoSOD seems to be of entropic origin due to increased loop flexibility in the monomeric state: in the disulphide-reduced holo protein this gain in configurational entropy upon splitting of the dimer interface is reduced by the metal coordination.

Publiceringsår

2007

Språk

Engelska

Sidor

333-342

Publikation/Tidskrift/Serie

Journal of Molecular Biology

Volym

365

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Biological Sciences

Nyckelord

  • loop entropy
  • dimerisation
  • disulphide bond
  • ALS
  • protein folding

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1089-8638