TY - JOUR
T1 - Targeting and maturation of Erv1/ALR in the mitochondrial intermembrane space
AU - Kallergi, Emmanouela
AU - Andreadaki, Maria
AU - Kritsiligkou, Paraskevi
AU - Katrakili, Nitsa
AU - Pozidis, Charalambos
AU - Tokatlidis, Kostas
AU - Banci, Lucia
AU - Bertini, Ivano
AU - Cefaro, Chiara
AU - Ciofi-Baffoni, Simone
AU - Gajda, Karolina
AU - Peruzzini, Riccardo
PY - 2012/4/20
Y1 - 2012/4/20
N2 - The interaction of Mia40 with Erv1/ALR is central to the oxidative protein folding in the intermembrane space of mitochondria (IMS) as Erv1/ALR oxidizes reduced Mia40 to restore its functional state. Here we address the role of Mia40 in the import and maturation of Erv1/ALR. The C-terminal FAD-binding domain of Erv1/ALR has an essential role in the import process by creating a transient intermolecular disulfide bond with Mia40. The action of Mia40 is selective for the formation of both intra and intersubunit structural disulfide bonds of Erv1/ALR, but the complete maturation process requires additional binding of FAD. Both of these events must follow a specific sequential order to allow Erv1/ALR to reach the fully functional state, illustrating a new paradigm for protein maturation in the IMS.
AB - The interaction of Mia40 with Erv1/ALR is central to the oxidative protein folding in the intermembrane space of mitochondria (IMS) as Erv1/ALR oxidizes reduced Mia40 to restore its functional state. Here we address the role of Mia40 in the import and maturation of Erv1/ALR. The C-terminal FAD-binding domain of Erv1/ALR has an essential role in the import process by creating a transient intermolecular disulfide bond with Mia40. The action of Mia40 is selective for the formation of both intra and intersubunit structural disulfide bonds of Erv1/ALR, but the complete maturation process requires additional binding of FAD. Both of these events must follow a specific sequential order to allow Erv1/ALR to reach the fully functional state, illustrating a new paradigm for protein maturation in the IMS.
KW - Cytochrome Reductases
KW - Disulfides
KW - Flavin-Adenine Dinucleotide
KW - Humans
KW - Mitochondrial Membrane Transport Proteins
KW - Mitochondrial Membranes
KW - Protein Folding
KW - Protein Transport
U2 - 10.1021/cb200485b
DO - 10.1021/cb200485b
M3 - Article
C2 - 22296668
SN - 1554-8929
VL - 7
SP - 707
EP - 714
JO - ACS chemical biology
JF - ACS chemical biology
IS - 4
ER -