Epitopes described in "Characterization of conformation-dependent prion protein epitopes."

Article Authors:Hae-Eun Kang; Chu Chun Weng; Eri Saijo; Vicki Saylor; Jifeng Bian; Sehun Kim; Laylaa Ramos; Rachel Angers; Katie Langenfeld; Vadim Khaychuk; Carla Calvi; Jason Bartz; Nora Hunter; Glenn C Telling
Article Title:Characterization of conformation-dependent prion protein epitopes.
Reference Detail
Reference ID:1025257
Abstract:Whereas prion replication involves structural rearrangement of cellular prion protein (PrP(C)), the existence of conformational epitopes remains speculative and controversial, and PrP transformation is monitored by immunoblot detection of PrP(27-30), a protease-resistant counterpart of the pathogenic scrapie form (PrP(Sc)) of PrP. We now describe the involvement of specific amino acids in conformational determinants of novel monoclonal antibodies (mAbs) raised against randomly chimeric PrP. Epitope recognition of two mAbs depended on polymorphisms controlling disease susceptibility. Detection by one, referred to as PRC5, required alanine and asparagine at discontinuous mouse PrP residues 132 and 158, which acquire proximity when residues 126-218 form a structured globular domain. The discontinuous epitope of glycosylation-dependent mAb PRC7 also mapped within this domain at residues 154 and 185. In accordance with their conformational dependence, tertiary structure perturbations compromised recognition by PRC5, PRC7, as well as previously characterized mAbs whose epitopes also reside in the globular domain, whereas conformation-independent epitopes proximal or distal to this region were refractory to such destabilizing treatments. Our studies also address the paradox of how conformational epitopes remain functional following denaturing treatments and indicate that cellular PrP and PrP(27-30) both renature to a common structure that reconstitutes the globular domain.
Affiliations:Prion Research Center, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523, USA.
Reference Type:Literature
PubMed ID:22948149
Journal:J Biol Chem
Journal Volume:287
Article Pages:37219-32
Journal ISSN:0021-9258
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5b81ab48;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1e1432e7;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4019eb1e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@659b1f72;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2b2da97b
Article MeSH List:Amino Acid Sequence; Animals; Antibodies, Monoclonal, Murine-Derived(biosynthesis; isolation & purification); Cattle; Conserved Sequence; Deer; Directed Molecular Evolution; Epitope Mapping; Epitopes(chemistry; genetics; immunology); Humans; Hybridomas; Mice; Mice, Transgenic; Models, Molecular; Molecular Sequence Data; Oxidation-Reduction; PrPC Proteins(chemistry; genetics; immunology); PrPSc Proteins(chemistry; genetics; immunology); Protein Binding; Protein Structure, Tertiary; Recombinant Fusion Proteins(genetics; immunology); Saimiri; Sequence Deletion; Sheep
Curation Last Updated:2015-01-18 00:35:04