6SV2

Human prion protein (PrP) fragment 119-231 (G127V M129 variant) complexed to ICSM 18 (anti-Prp therapeutic antibody) Fab fragment

Summary for 6SV2

• Entry DOI: 10.2210/pdb6sv2/pdb
• Related: 6SUZ
• Descriptor: ICSM 18-ANTI-PRP THERAPEUTIC FAB LIGHT CHAIN, ICSM 18-ANTI-PRP THERAPEUTIC FAB HEAVY CHAIN, Major prion protein, ... (5 entities in total)
• Functional Keywords: prion, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 59699.12

Authors

Conners, R. (deposition date: 2019-09-17, release date: 2020-07-29, Last modification date: 2024-11-20)

Primary citation

Hosszu, L.L.P.,Conners, R.,Sangar, D.,Batchelor, M.,Sawyer, E.B.,Fisher, S.,Cliff, M.J.,Hounslow, A.M.,McAuley, K.,Leo Brady, R.,Jackson, G.S.,Bieschke, J.,Waltho, J.P.,Collinge, J.
Structural effects of the highly protective V127 polymorphism on human prion protein.
Commun Biol, 3:402-402, 2020

PubMed Abstract: Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.

PubMed: 32728168
DOI: 10.1038/s42003-020-01126-6

Experimental method

X-RAY DIFFRACTION (2.3 Å)