scholarly journals Probing the N-Terminal β-Sheet Conversion in the Crystal Structure of the Human Prion Protein Bound to a Nanobody

2014 ◽  
Vol 136 (3) ◽  
pp. 937-944 ◽  
Author(s):  
Romany N. N. Abskharon ◽  
Gabriele Giachin ◽  
Alexandre Wohlkonig ◽  
Sameh H. Soror ◽  
Els Pardon ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Prion Protein ◽  
Human Prion Protein ◽  
Β Sheet

scholarly journals Crystal structure of human prion protein bound to a therapeutic antibody

2009 ◽  
Vol 106 (8) ◽  
pp. 2554-2558 ◽  
Author(s):  
S. V. Antonyuk ◽  
C. R. Trevitt ◽  
R. W. Strange ◽  
G. S. Jackson ◽  
D. Sangar ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Prion Protein ◽  
Therapeutic Antibody ◽  
Human Prion Protein

scholarly journals Polymorphism at 129 dictates metastable conformations of the human prion protein N-terminal β-sheet

2017 ◽  
Vol 8 (2) ◽  
pp. 1225-1232 ◽  
Author(s):  
S. Alexis Paz ◽  
Eric Vanden-Eijnden ◽  
Cameron F. Abrams
Keyword(s):  
Free Energy ◽  
Prion Protein ◽  
Thermodynamic Stability ◽  
Energy Method ◽  
Replica Exchange ◽  
Native State ◽  
Human Prion Protein ◽  
Β Sheet

We study the thermodynamic stability of the native state of the human prion protein using a new free-energy method, replica-exchange on-the-fly parameterization.

scholarly journals Diverse Effects on the Native β-Sheet of the Human Prion Protein Due to Disease-Associated Mutations

Biochemistry ◽  
2010 ◽  
Vol 49 (45) ◽  
pp. 9874-9881 ◽  
Author(s):  
Wei Chen ◽  
Marc W. van der Kamp ◽  
Valerie Daggett
Keyword(s):  
Prion Protein ◽  
Human Prion Protein ◽  
Β Sheet

scholarly journals Structural studies on the folded domain of the human prion protein bound to the Fab fragment of the antibody POM1

2012 ◽  
Vol 68 (11) ◽  
pp. 1501-1512 ◽  
Author(s):  
Pravas Kumar Baral ◽  
Barbara Wieland ◽  
Mridula Swayampakula ◽  
Magdalini Polymenidou ◽  
Muhammad Hafiz Rahman ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Prion Protein ◽  
Prion Diseases ◽  
Passive Immunization ◽  
Antibody Fragment ◽  
Binding Mode ◽  
Cellular Prion Protein ◽  
Fab Fragment ◽  
Human Prion Protein

Prion diseases are neurodegenerative diseases characterized by the conversion of the cellular prion protein PrPcinto a pathogenic isoform PrPsc. Passive immunization with antiprion monoclonal antibodies can arrest the progression of prion diseases. Here, the crystal structure of the Fab fragment of an antiprion monoclonal antibody, POM1, in complex with human prion protein (huPrPc) has been determined to 2.4 Å resolution. The prion epitope of POM1 is in close proximity to the epitope recognized by the purportedly therapeutic antibody fragment ICSM18 Fab in complex with huPrPc. POM1 Fab forms a 1:1 complex with huPrPcand the measuredKdof 4.5 × 10−7 Mreveals moderately strong binding between them. Structural comparisons have been made among three prion–antibody complexes: POM1 Fab–huPrPc, ICSM18 Fab–huPrPcand VRQ14 Fab–ovPrPc. The prion epitopes recognized by ICSM18 Fab and VRQ14 Fab are adjacent to a prion glycosylation site, indicating possible steric hindrance and/or an altered binding mode to the glycosylated prion proteinin vivo. However, both of the glycosylation sites on huPrPcare positioned away from the POM1 Fab binding epitope; thus, the binding mode observed in this crystal structure and the binding affinity measured for this antibody are most likely to be the same as those for the native prion proteinin vivo.

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