Your browser doesn't support javascript.
loading
Molecular basis for plasma membrane recruitment of PI4KA by EFR3.
Suresh, Sushant; Shaw, Alexandria L; Pemberton, Joshua G; Scott, Mackenzie K; Harris, Noah J; Parson, Matthew Ah; Jenkins, Meredith L; Rohilla, Pooja; Alvarez-Prats, Alejandro; Balla, Tamas; Yip, Calvin K; Burke, John E.
Afiliación
  • Suresh S; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
  • Shaw AL; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
  • Pemberton JG; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
  • Scott MK; Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
  • Harris NJ; Current address: Department of Biology, Western University, London, ON, N6A 3K7 Canada.
  • Parson MA; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
  • Jenkins ML; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
  • Rohilla P; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
  • Alvarez-Prats A; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
  • Balla T; Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
  • Yip CK; Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
  • Burke JE; Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
bioRxiv ; 2024 Jul 19.
Article en En | MEDLINE | ID: mdl-38746453
ABSTRACT
The lipid kinase phosphatidylinositol 4 kinase III alpha (PI4KIIIa/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B. Here, we report a cryo-EM structure of the C-terminus of EFR3A bound to the PI4KA-TTC7B-FAM126A complex, with extensive validation using both hydrogen deuterium exchange mass spectrometry (HDX-MS), and mutational analysis. The EFR3A C-terminus undergoes a disorder-order transition upon binding to the PI4KA complex, with an unexpected direct interaction with both TTC7B and FAM126A. Complex disrupting mutations in TTC7B, FAM126A, and EFR3 decrease PI4KA recruitment to the plasma membrane. Multiple post-translational modifications and disease linked mutations map to this site, providing insight into how PI4KA membrane recruitment can be regulated and disrupted in human disease.
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos