Prion: Gene, Structure, and Species Barrier
-
Sherman Jew
Hypothesis: Prion species barrier may be due to genetic variation and protein structural differences among different species.
Methods: Sequence analyses of open reading frames of the prion gene from different species, including human, deer, sheep, cattle, mouse, and rat were conducted. Synthetic prion-derived peptides with strategic point mutations were manufactured and studied to investigate potential conformational changes.
Results: Codon 129 is a polymorphism position where, in the human population, 50% is Met (Methionine)/Val (Valine), 40% Met/Met, 10% Val/Val. Other species: sheep, cattle, rat, and mouse have a conserved codon 129 with Met/Met. It is observed that with Met at codon 129, transmission of prion disorder is relatively consistent regarding incubation time. However, if codon 129 is other than Met, eg, Valine in rat, Leucine (Leu) in Wapiti deer, incubation time of prion disorder is inconsistent or prolonged. Furthermore, there are four putative alpha-helical regions forming four-helix bundles in the prion protein which are proposed to be critical in the stability of the protein. If these alpha-helical regions convert to beta-pleated sheets, the altered prion protein accumulates in the brain tissues and degenerative changes occur. Prion-derived peptide 121-231, containing Met at codon 129, demonstrated alpha-helical conformation under nuclear magnetic resonance (NMR). However, if Val or Leu is at codon 129, prion-derived peptide 121-231 demonstrated beta-pleated sheet conformation under NMR analysis.
Conclusions: Prion species barrier may be, at least in part, explained by differences in genetic and/or protein structural variations among different species.
-
Sponsors: Patricia Hentosh, ScD, and Paul Dew, MD, MPH, at Kansas City (Mo) University of Medicine and Biosciences; Stanley Prusiner, MD, at University of California, San Francisco.
The American Osteopathic Association
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles in the same Issue
- LETTERS
- Final Notes From the Chief of Staff
- CORRECTIONS
- Correction
- ORIGINAL CONTRIBUTIONS
- Effects of Osteopathic Manipulative Treatment on Pediatric Patients With Asthma: A Randomized Controlled Trial
- CLINICAL PRACTICE
- Patient-Physician Communication: Why and How
- STUDENT CONTRIBUTIONS
- Student Involvement in Research
- Tendon Gene Therapy Modulates the Local Repair Environment in the Shoulder
- A Theoretical Study of Polarization Effects on a Model Peptide Bond
- Assessment of Patient Flow in Routine Office Visits: Perspectives on Minimizing Patient Visiting Time
- Hysteresis as a Measure of Ankle Dysfunction
- Prion: Gene, Structure, and Species Barrier
- Outpatient Prescribing Practices for Nonapproved Drugs in Children
- Is Equity Being Sacrificed? The Effect of User Fees on the Willingness and ability to pay for Schistosomiasis Control in the Lake Victoria Region of Tanzania
- A Pilot Study Examining the Effects of Neuromuscular Therapy on Patients With Parkinson's Disease
- Metabolic Syndrome and Postoperative Complications in Cardiothoracic and Vascular Surgical and Percutaneous Interventions
- Blood Glucose Correlations With Depression, Body Habitus and Caregiving Status in the Elderly Kenyan Luo Grandparents
- VOLUME 104 INDEX
- Author Index
- CME QUIZ
- CME Quiz
Articles in the same Issue
- LETTERS
- Final Notes From the Chief of Staff
- CORRECTIONS
- Correction
- ORIGINAL CONTRIBUTIONS
- Effects of Osteopathic Manipulative Treatment on Pediatric Patients With Asthma: A Randomized Controlled Trial
- CLINICAL PRACTICE
- Patient-Physician Communication: Why and How
- STUDENT CONTRIBUTIONS
- Student Involvement in Research
- Tendon Gene Therapy Modulates the Local Repair Environment in the Shoulder
- A Theoretical Study of Polarization Effects on a Model Peptide Bond
- Assessment of Patient Flow in Routine Office Visits: Perspectives on Minimizing Patient Visiting Time
- Hysteresis as a Measure of Ankle Dysfunction
- Prion: Gene, Structure, and Species Barrier
- Outpatient Prescribing Practices for Nonapproved Drugs in Children
- Is Equity Being Sacrificed? The Effect of User Fees on the Willingness and ability to pay for Schistosomiasis Control in the Lake Victoria Region of Tanzania
- A Pilot Study Examining the Effects of Neuromuscular Therapy on Patients With Parkinson's Disease
- Metabolic Syndrome and Postoperative Complications in Cardiothoracic and Vascular Surgical and Percutaneous Interventions
- Blood Glucose Correlations With Depression, Body Habitus and Caregiving Status in the Elderly Kenyan Luo Grandparents
- VOLUME 104 INDEX
- Author Index
- CME QUIZ
- CME Quiz
