Structural mapping of missense mutations in the Pex1/Pex6 complex
- 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 forPeroxisome 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.…
Verfasserangaben: | Anne Schieferdecker, Petra WendlerORCiDGND |
---|---|
URN: | urn:nbn:de:kobv:517-opus4-472843 |
DOI: | https://doi.org/10.25932/publishup-47284 |
ISSN: | 1866-8372 |
Titel des übergeordneten Werks (Deutsch): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1072) |
Publikationstyp: | Postprint |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 07.01.2021 |
Erscheinungsjahr: | 2019 |
Veröffentlichende Institution: | Universität Potsdam |
Datum der Freischaltung: | 07.01.2021 |
Freies Schlagwort / Tag: | Pex1; Pex6; Zellweger; Zellweger syndrome spectrum disorder (ZSSD); mutation; structure |
Ausgabe: | 1072 |
Seitenanzahl: | 27 |
Quelle: | International Journal of Molecular Sciences 20 (2019) 15, Art. 3756 DOI: 10.3390/ijms20153756 |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät |
Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie | |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie | |
Peer Review: | Referiert |
Fördermittelquelle: | Multidisciplinary Digital Publishing Institute (MDPI) |
Publikationsweg: | Open Access / Green Open-Access |
Lizenz (Deutsch): | CC-BY - Namensnennung 4.0 International |
Externe Anmerkung: | Bibliographieeintrag der Originalveröffentlichung/Quelle |