Molecular dynamics studies on 3D structures of the hydrophobic region PrP(109-136)

Zhang, Jiapu; Zhang, Yuanli

doi:10.1093/abbs/gmt031

Cited by 22 publications

(19 citation statements)

References 67 publications

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“…Currently, there is no structural information about prion AGAAAAGA amyloid fibrils because of unstable, noncrystalline and insoluble nature of this region, though numerous laboratory experimental results have confirmed this region owning an amyloid fibril forming property (initially described in 1992 by Stanley B. Prusiner's group). We also did accurate computer calculations on this region and confirmed the amyloid fibril property in this palindrome region [67,73].…”

Section: The Hybrid Idea and Some Hybrid Optimization Methodssupporting

confidence: 56%

The Hybrid Idea of (Energy Minimization) Optimization Methods Applied to Study PrionProtein Structures Focusing on the beta2-alpha2 Loop

Zhang¹

2015

Biochem Pharmacol (Los Angel)

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In molecular mechanics, current generation potential energy functions provide a reasonably good compromise between accuracy and effectiveness. This paper firstly reviewed several most commonly used classical potential energy functions and their optimization methods used for energy minimization. To minimize a potential energy function, about 95% efforts are spent on the Lennard-Jones potential of van der Waals interactions; we also give a detailed review on some effective computational optimization methods in the Cambridge Cluster Database to solve the problem of Lennard-Jones clusters. From the reviews, we found the hybrid idea of optimization methods is effective, necessary and efficient for solving the potential energy minimization problem and the Lennard-Jones clusters problem. An application to prion protein structures is then done by the hybrid idea. We focus on the β2-α2 loop of prion protein structures, and we found (i) the species that has the clearly and highly ordered β2-α2 loop usually owns a 3 10 -helix in this loop, (ii) a "π-circle" Y128-F175-Y218-Y163-F175-Y169-R164-Y128(-Y162) is around the β2-α2 loop.

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Section: The Hybrid Idea and Some Hybrid Optimization Methodssupporting

confidence: 56%

The Hybrid Idea of (Energy Minimization) Optimization Methods Applied to Study PrionProtein Structures Focusing on the beta2-alpha2 Loop

Zhang¹

2015

Biochem Pharmacol (Los Angel)

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“…In the present study, the variant at codon 127 in particular was highly polymorphic. Amino acids at codon 126 and 127 are localized in the highly conserved glycine rich motif GAVVG 126 G 127 LGGYMLG.This residue was reported to antagonize prion disease development by blocking amyloidal fibril formation [2]. A recent work by Vitale et al,2019 reported polymorphism at this position and implicated its importance in the normal cellular function of prion protein [21].The sequence variation in palindrome residue (PrP 113-120 ) and glycine repeat regions (PrP 124-128 ) synergistically may affect cellular prion protein conformational flexibility.…”

Section: Discussionmentioning

confidence: 99%

Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds

Teferedegn

Yaman

Ün³

2020

Preprint

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Background: Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene (PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at position 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results : Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion: Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.

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“…The MD methods employed are the same as the previous studies (Zhang & Zhang, 2013Zhang, 2010Zhang, & 2011c. Briefly, all simulations used the ff03 force field of the AMBER 11 package (Case et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

A review on the salt bridge ASP177-ARG163 (O–N) of wild-type rabbit prion protein

Zhang

Wang

2016

Journal of Biomolecular Structure and Dynamics

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Abstract:Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elks, humans and mice etc., but rabbits have a low susceptibility to be infected by prion diseases with respect to other species. The stability of rabbit prion protein is due to its highly ordered β2-α2 loop (PLoS One 5(10) e13273 X-ray file of the rabbit prion protein, we can clearly observe this salt bridge. This article analyses the NMR and X-ray structures and gives an answer to the above question: the salt bridge presents at pH 6.5 in the X-ray structure is simply gone at pH 4.5 in the NMR structure is simply due to the different pH values that impact electrostatics at the salt bridge and hence also impact the structures. Moreover, some molecular dynamics simulation results of the X-ray structure are reported in this article to reveal the secrets of the structural stability of rabbit prion protein.

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Molecular dynamics studies on 3D structures of the hydrophobic region PrP(109-136)

Cited by 22 publications

References 67 publications

The Hybrid Idea of (Energy Minimization) Optimization Methods Applied to Study PrionProtein Structures Focusing on the beta2-alpha2 Loop

The Hybrid Idea of (Energy Minimization) Optimization Methods Applied to Study PrionProtein Structures Focusing on the beta2-alpha2 Loop

Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds

A review on the salt bridge ASP177-ARG163 (O–N) of wild-type rabbit prion protein

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