Molecular dynamics study of the metallochaperone Hah1 in its apo and Cu(I)-loaded states: role of the conserved residue M10.
Molecular dynamics simulations were performed on both apo and copper forms of the human copper chaperone, Hah1. Wild-type Hah1 and a methionine (M10) to serine mutant were investigated. We have evidenced the central role of residue M10 in stabilizing the hydrophobic core of Hah1 as well as the internal structure of the metal-binding site. When copper(I) is bound, the mobility of Hah1 is reduced whereas mutation of M10 implies a drastic increase of the mobility of apoHah1, stressing the importance of this highly conserved hydrophobic residue for copper sequestration by the apoprotein.
Poger
David
D
Laboratoire de Biophysique Moléculaire et Cellulaire, Département de Réponse et Dynamique Cellulaires, Commissariat à l'Energie Atomique, Grenoble, France.
Fuchs
Jean-François
JF
Nedev
Hristo
H
Ferrand
Michel
M
Crouzy
Serge
S
D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
C474500:ATOX1 protein, human; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D008670:Metals; D018832:Molecular Chaperones