4YXH

Crystal structure of Deer prion protein complexed with POM1 FAB

Summary for 4YXH

• Entry DOI: 10.2210/pdb4yxh/pdb
• Related: 4YX2 4YXK 4YXL
• Descriptor: Major prion protein, POM1 FAB HEAVY CHAIN, POM1 FAB LIGHT CHAIN, ... (5 entities in total)
• Functional Keywords: prion, antibody, immune system complex, immune system
• Biological source: Odocoileus hemionus (Mule deer); More
• Cellular location: Cell membrane ; Lipid-anchor, GPI-anchor : P47852
• Total number of polymer chains: 3
• Total formula weight: 62887.56

Authors

Baral, P.K.,Swayampakula, M.,James, M.N.G. (deposition date: 2015-03-23, release date: 2015-09-23, Last modification date: 2024-10-23)

Primary citation

Baral, P.K.,Swayampakula, M.,Aguzzi, A.,James, M.N.
X-ray structural and molecular dynamical studies of the globular domains of cow, deer, elk and Syrian hamster prion proteins.
J.Struct.Biol., 192:37-47, 2015

PubMed Abstract: Misfolded prion proteins are the cause of neurodegenerative diseases that affect many mammalian species, including humans. Transmission of the prion diseases poses a considerable public-health risk as a specific prion disease such as bovine spongiform encephalopathy can be transferred to humans and other mammalian species upon contaminant exposure. The underlying mechanism of prion propagation and the species barriers that control cross species transmission has been investigated quite extensively. So far a number of prion strains have been characterized and those have been intimately linked to species-specific infectivity and other pathophysiological manifestations. These strains are encoded by a protein-only agent, and have a high degree of sequence identity across mammalian species. The molecular events that lead to strain differentiation remain elusive. In order to contribute to the understanding of strain differentiation, we have determined the crystal structures of the globular, folded domains of four prion proteins (cow, deer, elk and Syrian hamster) bound to the POM1 antibody fragment Fab. Although the overall structural folds of the mammalian prion proteins remains extremely similar, there are several local structural variations observed in the misfolding-initiator motifs. In additional molecular dynamics simulation studies on these several prion proteins reveal differences in the local fluctuations and imply that these differences have possible roles in the unfolding of the globular domains. These local variations in the structured domains perpetuate diverse patterns of prion misfolding and possibly facilitate the strain selection and adaptation.

PubMed: 26320075
DOI: 10.1016/j.jsb.2015.08.014

Experimental method

X-RAY DIFFRACTION (2.7 Å)