Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent

Alakesh Bera, Pradip K. Nandi

Research output: Contribution to journalArticle

Abstract

Nucleic acid can catalyze the conversion of α-helical cellular prion protein to β-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered α-helical structure is considered to be a necessary step for the structural conversion to its β-sheet rich isoform, we have studied the unfolding of the α-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein.

Original languageEnglish (US)
Pages (from-to)1780-1788
Number of pages9
JournalProtein Science
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

Fingerprint

Recombinant Proteins
Nucleic Acids
Secondary Protein Structure
Protein Unfolding
Proteins
Endopeptidase K
Denaturation
Temperature
Prion Proteins
Prions
Oligomers
Amyloid
Polymers
Protein Isoforms
Hot Temperature
Molecules
Acids

Keywords

  • denaturation temperature (T<inf>m</inf>)
  • nucleic acids
  • pH 5
  • PloyA
  • prion protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent. / Bera, Alakesh; Nandi, Pradip K.

In: Protein Science, Vol. 23, No. 12, 01.12.2014, p. 1780-1788.

Research output: Contribution to journalArticle

Bera, Alakesh ; Nandi, Pradip K. / Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent. In: Protein Science. 2014 ; Vol. 23, No. 12. pp. 1780-1788.
@article{ed4caf98beea46e8bd96dc2beb817b69,
title = "Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent",
abstract = "Nucleic acid can catalyze the conversion of α-helical cellular prion protein to β-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered α-helical structure is considered to be a necessary step for the structural conversion to its β-sheet rich isoform, we have studied the unfolding of the α-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein.",
keywords = "denaturation temperature (T<inf>m</inf>), nucleic acids, pH 5, PloyA, prion protein",
author = "Alakesh Bera and Nandi, {Pradip K.}",
year = "2014",
month = "12",
day = "1",
doi = "10.1002/pro.2573",
language = "English (US)",
volume = "23",
pages = "1780--1788",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Cold Spring Harbor Laboratory Press",
number = "12",

}

TY - JOUR

T1 - Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent

AU - Bera, Alakesh

AU - Nandi, Pradip K.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Nucleic acid can catalyze the conversion of α-helical cellular prion protein to β-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered α-helical structure is considered to be a necessary step for the structural conversion to its β-sheet rich isoform, we have studied the unfolding of the α-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein.

AB - Nucleic acid can catalyze the conversion of α-helical cellular prion protein to β-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered α-helical structure is considered to be a necessary step for the structural conversion to its β-sheet rich isoform, we have studied the unfolding of the α-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein.

KW - denaturation temperature (T<inf>m</inf>)

KW - nucleic acids

KW - pH 5

KW - PloyA

KW - prion protein

UR - http://www.scopus.com/inward/record.url?scp=84928951141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928951141&partnerID=8YFLogxK

U2 - 10.1002/pro.2573

DO - 10.1002/pro.2573

M3 - Article

C2 - 25271002

AN - SCOPUS:84928951141

VL - 23

SP - 1780

EP - 1788

JO - Protein Science

JF - Protein Science

SN - 0961-8368

IS - 12

ER -