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Structural characterization of POM6 Fab and mouse prion protein complex identifies key regions for prions conformational conversion
- Source :
- The FEBS journal. 285(9)
- Publication Year :
- 2017
-
Abstract
- Conversion of the cellular prion protein PrPC into its pathogenic isoform PrPSc is the hallmark of prion diseases, fatal neurodegenerative diseases affecting many mammalian species including humans. Anti‐prion monoclonal antibodies can arrest the progression of prion diseases by stabilizing the cellular form of the prion protein. Here, we present the crystal structure of the POM6 Fab fragment, in complex with the mouse prion protein (moPrP). The prion epitope of POM6 is in close proximity to the epitope recognized by the purportedly toxic antibody fragment, POM1 Fab also complexed with moPrP. The POM6 Fab recognizes a larger binding interface indicating a likely stronger binding compared to POM1. POM6 and POM1 exhibit distinct biological responses. Structural comparisons of the bound mouse prion proteins from the POM6 Fab:moPrP and POM1 Fab:moPrP complexes reveal several key regions of the prion protein that might be involved in initiating mis‐folding events.
- Subjects :
- 0301 basic medicine
Gene isoform
Models, Molecular
Protein Folding
Glycosylation
medicine.drug_class
Protein Conformation
animal diseases
Static Electricity
Monoclonal antibody
Crystallography, X-Ray
Biochemistry
Epitope
Pom1
Antigen-Antibody Reactions
03 medical and health sciences
Immunoglobulin Fab Fragments
Mice
Immune system
medicine
Animals
PrPC Proteins
Prion protein
Molecular Biology
biology
Chemistry
Antibodies, Monoclonal
Cell Biology
nervous system diseases
Cell biology
030104 developmental biology
biology.protein
Antibody
Prion Proteins
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 17424658
- Volume :
- 285
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- The FEBS journal
- Accession number :
- edsair.doi.dedup.....c9d6d3126fedff0b555a0ca28fc3de1e