The role of protonation in protein fibrillation

Martin D Jeppesen; Peter Westh; Daniel E Otzen

doi:10.1016/j.febslet.2010.01.002

The role of protonation in protein fibrillation

Martin D Jeppesen, Peter Westh, Daniel E Otzen

Department of Chemistry - Center for Uopløselige Proteinstrukturer

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

25 Citations (Scopus)

Abstract

Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pK(a) values change dramatically in the fibrillar state.

Original language	English
Journal	FEBS Letters
Volume	584
Issue	4
Pages (from-to)	780-4
Number of pages	5
DOIs	https://doi.org/10.1016/j.febslet.2010.01.002
Publication status	Published - 19 Feb 2010

Keywords

Buffers
Calorimetry
Circular Dichroism
Glucagon
Hydrogen-Ion Concentration
Kinetics
Microscopy, Atomic Force
Models, Chemical
Muramidase
Protein Folding
Proteins
Protons
Thermodynamics
Titrimetry

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10.1016/j.febslet.2010.01.002

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title = "The role of protonation in protein fibrillation",

abstract = "Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pK(a) values change dramatically in the fibrillar state.",

keywords = "Buffers, Calorimetry, Circular Dichroism, Glucagon, Hydrogen-Ion Concentration, Kinetics, Microscopy, Atomic Force, Models, Chemical, Muramidase, Protein Folding, Proteins, Protons, Thermodynamics, Titrimetry",

author = "Jeppesen, {Martin D} and Peter Westh and Otzen, {Daniel E}",

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doi = "10.1016/j.febslet.2010.01.002",

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volume = "584",

pages = "780--4",

journal = "FEBS Letters",

issn = "1873-3468",

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TY - JOUR

T1 - The role of protonation in protein fibrillation

AU - Jeppesen, Martin D

AU - Westh, Peter

AU - Otzen, Daniel E

PY - 2010/2/19

Y1 - 2010/2/19

N2 - Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pK(a) values change dramatically in the fibrillar state.

AB - Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pK(a) values change dramatically in the fibrillar state.

KW - Buffers

KW - Calorimetry

KW - Circular Dichroism

KW - Glucagon

KW - Hydrogen-Ion Concentration

KW - Kinetics

KW - Microscopy, Atomic Force

KW - Models, Chemical

KW - Muramidase

KW - Protein Folding

KW - Proteins

KW - Protons

KW - Thermodynamics

KW - Titrimetry

U2 - 10.1016/j.febslet.2010.01.002

DO - 10.1016/j.febslet.2010.01.002

M3 - Journal article

C2 - 20067793

SN - 1873-3468

VL - 584

SP - 780

EP - 784

JO - FEBS Letters

JF - FEBS Letters

IS - 4

ER -

The role of protonation in protein fibrillation

Abstract

Keywords

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