TY  - JOUR
A1  - Schieferdecker, Anne
A1  - Wendler, Petra
T1  - Structural Mapping of Missense Mutations in the Pex1/Pex6 Complex
JF  - International journal of molecular sciences
N2  - Peroxisome biogenesis disorders (PBDs) are nontreatable hereditary diseases with a broad range of severity. Approximately 65% of patients are affected by mutations in the peroxins Pex1 and Pex6. The proteins form the heteromeric Pex1/Pex6 complex, which is important for protein import into peroxisomes. To date, no structural data are available for this AAA+ ATPase complex. However, a wealth of information can be transferred from low-resolution structures of the yeast scPex1/scPex6 complex and homologous, well-characterized AAA+ ATPases. We review the abundant records of missense mutations described in PBD patients with the aim to classify and rationalize them by mapping them onto a homology model of the human Pex1/Pex6 complex. Several mutations concern functionally conserved residues that are implied in ATP hydrolysis and substrate processing. Contrary to fold destabilizing mutations, patients suffering from function-impairing mutations may not benefit from stabilizing agents, which have been reported as potential therapeutics for PBD patients.
KW  - Zellweger syndrome spectrum disorder (ZSSD)
KW  - Zellweger
KW  - structure
KW  - Pex1
KW  - Pex6
KW  - mutation
Y1  - 2019
U6  - https://doi.org/10.3390/ijms20153756
SN  - 1422-0067
VL  - 20
IS  - 15
PB  - MDPI
CY  - Basel
ER  -