umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Differential Roles of Met10, Thr11, and Lys60 in Structural Dynamics of Human Copper Chaperone Atox1
Umeå universitet, Teknisk-naturvetenskaplig fakultet, Kemi.
2009 (Engelska)Ingår i: BIOCHEMISTRY including biophysical chemistry & molecular biology, Vol. 48, nr 5, s. 960-72Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Atox1 is a human copper (Cu) chaperone with the ferredoxin-like fold that binds Cu(I) via two Cys residues in a M10X11C12X13X14C15 motif located in a solvent-exposed loop. Here, we report molecular dynamics simulations that reveal the roles of Met10, Thr11, and Lys60 in Atox1 structural dynamics. Whereas Met10 is conserved in all Atox1 homologues, Thr11 and Lys60 are exchanged for Ser and Tyr in bacteria. From simulations on apo and Cu(I) forms of Met10Ala, Thr11Ala, Lys60Ala, Thr11Ser, and Lys60Tyr variants, we have compared a range of structural and dynamic parameters such as backbone/Cu-loop dynamics, Cys solvent exposure, Cys-Cys distances, and cross-correlated motions. Surprisingly, Atox1 becomes more rigid in the absence of either Thr11 or Lys60, suggesting that these residues introduce protein flexibility. Lys60 and Thr11 also participate in electrostatic networks that stabilize the Cu-bound form and, in the apo form, determine the solvent exposure of the two Cys residues. In contrast, Met10 is buried in the hydrophobic core of Atox1, and its removal results in a dynamic protein structure. Prokaryotic residues are not good substitutes for the eukaryotic counterparts implying early divergence of Cu chaperone homologues. It appears that Atox1 residues have been conserved to ensure backbone/loop flexibility, electrostatic Cu site stabilization, and proper core packing. The discovered built-in flexibility may be directly linked to structural changes needed to form transient Atox1-Cu-target complexes in vivo.

Ort, förlag, år, upplaga, sidor
Washington: ACS Publications , 2009. Vol. 48, nr 5, s. 960-72
Identifikatorer
URN: urn:nbn:se:umu:diva-11576DOI: doi:10.1021/bi8018652OAI: oai:DiVA.org:umu-11576DiVA, id: diva2:151247
Tillgänglig från: 2009-01-16 Skapad: 2009-01-16 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltext

Personposter BETA

Wittung-Stafshede, Pernilla

Sök vidare i DiVA

Av författaren/redaktören
Wittung-Stafshede, Pernilla
Av organisationen
Kemi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 88 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf