Structural Mapping of Missense Mutations in the Pex1/Pex6 Complex.
Int J Mol Sci
; 20(15)2019 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-31374812
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastorno Peroxisomal
/
Mutación Missense
/
ATPasas Asociadas con Actividades Celulares Diversas
/
Proteínas de la Membrana
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania