The chemistry of copper binding to PrP: is there sufficient evidence to elucidate a role for copper in protein function?

2008 ◽  
Vol 410 (2) ◽  
pp. 237-244 ◽  
Author(s):  
Paul Davies ◽  
David R. Brown
Keyword(s):  
Prion Protein ◽  
Protein Function ◽  
Present Review ◽  
Sufficient Evidence ◽  
Copper Binding

There has been an enormous body of literature published in the last 10 years concerning copper and PrP (prion protein). Despite this, there is still no generally accepted role for copper in the function of PrP or any real consensus as to how and to what affinity copper associates with the protein. The present review attempts to look at all the evidence for the chemistry, co-ordination and affinity of copper binding to PrP, and then looks at what effect this has on the protein. We then connect this evidence with possible roles for PrP when bound to copper. No clear conclusions can be made from the available data, but it is clear from the present review what aspects of copper association with PrP need to be re-investigated.

Copper Binding Regulates Cellular Prion Protein Function

2019 ◽  
Vol 56 (9) ◽  
pp. 6121-6133 ◽  
Author(s):  
Xuan T. A. Nguyen ◽  
Thanh Hoa Tran ◽  
Dan Cojoc ◽  
Giuseppe Legname
Keyword(s):  
Prion Protein ◽  
Protein Function ◽  
Cellular Prion Protein ◽  
Copper Binding

scholarly journals Copper Binding Regulates Cellular Prion Protein Function

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Xuan T. A. Nguyen ◽  
Hoa T. Tran ◽  
Dan Cojoc ◽  
Giuseppe Legname
Keyword(s):  
Prion Protein ◽  
Protein Function ◽  
Cellular Prion Protein ◽  
Copper Binding

Metallic prions

2004 ◽  
Vol 71 ◽  
pp. 193-202 ◽  
Author(s):  
David R Brown
Keyword(s):  
Prion Protein ◽  
Binding Capacity ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Published Data ◽  
Normal Brain ◽  
Copper Binding ◽  
Loss Of Function ◽  
Spongiform Encephalopathies ◽  
The Brain

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. To this end much work has focused on elucidation of the normal function and activity of PrPc. Substantial evidence supports the notion that PrPc is a copper-binding protein. In conversion to the abnormal isoform, this Cu-binding activity is lost. Instead, there are some suggestions that the protein might bind other metals such as Mn or Zn. PrPc functions currently under investigation include the possibility that the protein is involved in signal transduction, cell adhesion, Cu transport and resistance to oxidative stress. Of these possibilities, only a role in Cu transport and its action as an antioxidant take into consideration PrPc's Cu-binding capacity. There are also more published data supporting these two functions. There is strong evidence that during the course of prion disease, there is a loss of function of the prion protein. This manifests as a change in metal balance in the brain and other organs and substantial oxidative damage throughout the brain. Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies.

scholarly journals Function Prediction from Protein Primary Structure using Deep Learning LSTM Algorithm

2019 ◽  
Vol 8 (4) ◽  
pp. 4355-4359
Keyword(s):  
Nervous System ◽  
Prion Protein ◽  
Primary Structure ◽  
Protein Function ◽  
Function Prediction ◽  
Biological Information ◽  
Essential Information ◽  
Diverse Field ◽  
Protein Primary Structure ◽  
And Function

Biological information of protein primary structure is responsible for finding the protein function, extracting features and function of a protein in the biology lab is challenging and time-consuming. Identification of protein function provides essential information for the treatment of various diseases and drug design. Therefore, extracting the protein knowledge from primary structure alone has been a diverse field in the study of bioinformatics data mining and computational biology. This study aimed to function prediction of protein primary structure using the LSTM methods. PRNP(prion protein )most of the nervous system tissues express by prion protein, this is generally to protease-resistant from disease, due to this reasons, the human codon PRNP is most closely associated with Alzheimer disease. The PRNP protein data trained with Hemo sapiens PRNP selection, classification was implemented with network layer perceptron. The learning algorithms are frame by the nervous system. The training results observation indicate that the learning success of prion protein classification leads positively.

scholarly journals The Prion Protein is a Combined Zinc and Copper Binding Protein:  Zn2+Alters the Distribution of Cu2+Coordination Modes

2007 ◽  
Vol 129 (50) ◽  
pp. 15440-15441 ◽  
Author(s):  
Eric D. Walter ◽  
Daniel J. Stevens ◽  
Micah P. Visconte ◽  
Glenn L. Millhauser
Keyword(s):  
Prion Protein ◽  
Binding Protein ◽  
Copper Binding ◽  
Coordination Modes ◽  
Copper Binding Protein

scholarly journals Prion Protein Expression in Human Leukocyte Differentiation

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1556-1561 ◽  
Author(s):  
Vincent C. Dodelet ◽  
Neil R. Cashman
Keyword(s):  
Retinoic Acid ◽  
Prion Protein ◽  
Protein Function ◽  
Mononuclear Cells ◽  
Prion Diseases ◽  
Expression Patterns ◽  
Human Leukocyte ◽  
Stem Cell Marker ◽  
Outer Leaflet

Abstract The cellular isoform of the prion protein (PrPC) is a small glycoprotein attached to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol anchor. This molecule is involved in the pathogenesis of prion diseases in both humans and animals. We have characterized the expression patterns of PrPC during human leukocyte maturation by flow cytometry with monoclonal antibodies to PrPC, the glycan moiety CD15, and the stem cell marker CD34. We observe that prion protein is present on CD34+bone marrow (BM) stem cells. Although lymphocytes and monocytes maintain PrPC expression throughout their differentiation, PrPC is downregulated upon differentiation along the granulocyte lineage. In vitro retinoic acid–induced differentiation of the premyeloid line HL-60 into granulocyte-like cells mimics the suppression of PrPC in granulocyte differentiation, as both PrPC mRNA and protein are downregulated. These data suggest that selected BM cells and peripheral mononuclear cells may support prion agent replication, because this process is dependent on availability of PrPC. Additionally, retinoic acid–induced extinction of PrPC expression in HL-60 cells provides a potential model to study PrP gene regulation and protein function. Finally, these data suggest the existence of cell-specific glycoforms of PrPC that may determine cellular susceptibility to infection by the prion agent.

Trace elements and prion diseases: a review of the interactions of copper, manganese and zinc with the prion protein

2006 ◽  
Vol 7 (1-2) ◽  
pp. 97-105 ◽  
Author(s):  
Scott P. Leach ◽  
M. D. Salman ◽  
Dwayne Hamar
Keyword(s):  
Trace Elements ◽  
Prion Protein ◽  
Copper Ions ◽  
Prion Diseases ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Copper Binding ◽  
Spongiform Encephalopathies ◽  
Copper Manganese ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative diseases characterized by their long incubation periods, progressive neurological changes, and spongiform appearance in the brain. There is much evidence to show that TSEs are caused by an isoform of the normal cellular surface prion protein PrPC. The normal function of PrPC is still unknown, but it exhibits properties of a cupro-protein, capable of binding up to six copper ions. There are two differing views on copper's role in prion diseases. While one view looks at the PrPC copper-binding as the trigger for conversion to PrPSc, the opposing viewpoint sees a lack of PrPC copper-binding resulting in the conformational change into the disease causing isoform. Manganese and zinc have been shown to interact with PrPC as well and have been found in abnormal levels in prion diseases. This review addresses the interaction between select trace elements and the PrPC.

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