Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein

Esther M. Martin, Frances D.L. Kondrat, Alan J. Stewart, James H. Scrivens, Peter J. Sadler, Claudia A. Blindauer

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)
20 Downloads (Pure)

Abstract

Zinc modulates the biological function of histidine-rich glycoprotein (HRG) through binding to its His-rich region (HRR). The Zn2+-binding properties of a 35 amino-acid biologically-active peptide mimic of the HRR, HRGP330, were investigated using dissociative mass spectrometry approaches in addition to travelling-wave ion mobility mass spectrometry (TWIM-MS). Native mass spectrometry confirmed zinc binding to HRGP330; however, broadening of the 1H NMR resonances upon addition of Zn2+ ions precluded the attainment of structural information. A complementary approach employing TWIM-MS indicated that HRGP330 has a more compact structure in the presence of Zn2+ ions. Top-down MS/MS data supported a metal-binding-induced conformational change, as fewer fragments were observed for Zn2+-bound HRGP330. Zn2+-bound fragments of both N-terminal and C-terminal ends of the peptide were identified from collision-induced dissociation (CID) and electron transfer dissociation/proton transfer reaction (ETD/PTR) experiments, suggesting that multiple binding sites exist within this region of HRG. The combination of mass spectrometry and NMR approaches provides new insight into the highly dynamic interaction between zinc and this His-rich peptide.

Original languageEnglish
Article number8646
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 5 Jun 2018

Fingerprint

Angiogenic Proteins
Mass spectrometry
Zinc
Ions
Peptides
Nuclear magnetic resonance
Proton transfer
Metals
Binding Sites
histidine-rich proteins
Amino Acids
Electrons

Cite this

Martin, Esther M. ; Kondrat, Frances D.L. ; Stewart, Alan J. ; Scrivens, James H. ; Sadler, Peter J. ; Blindauer, Claudia A. / Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{0eff07c0eaef46609b0eddb6cd1d4a26,
title = "Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein",
abstract = "Zinc modulates the biological function of histidine-rich glycoprotein (HRG) through binding to its His-rich region (HRR). The Zn2+-binding properties of a 35 amino-acid biologically-active peptide mimic of the HRR, HRGP330, were investigated using dissociative mass spectrometry approaches in addition to travelling-wave ion mobility mass spectrometry (TWIM-MS). Native mass spectrometry confirmed zinc binding to HRGP330; however, broadening of the 1H NMR resonances upon addition of Zn2+ ions precluded the attainment of structural information. A complementary approach employing TWIM-MS indicated that HRGP330 has a more compact structure in the presence of Zn2+ ions. Top-down MS/MS data supported a metal-binding-induced conformational change, as fewer fragments were observed for Zn2+-bound HRGP330. Zn2+-bound fragments of both N-terminal and C-terminal ends of the peptide were identified from collision-induced dissociation (CID) and electron transfer dissociation/proton transfer reaction (ETD/PTR) experiments, suggesting that multiple binding sites exist within this region of HRG. The combination of mass spectrometry and NMR approaches provides new insight into the highly dynamic interaction between zinc and this His-rich peptide.",
author = "Martin, {Esther M.} and Kondrat, {Frances D.L.} and Stewart, {Alan J.} and Scrivens, {James H.} and Sadler, {Peter J.} and Blindauer, {Claudia A.}",
year = "2018",
month = "6",
day = "5",
doi = "10.1038/s41598-018-26924-1",
language = "English",
volume = "8",
journal = "Nature Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein. / Martin, Esther M.; Kondrat, Frances D.L.; Stewart, Alan J.; Scrivens, James H.; Sadler, Peter J.; Blindauer, Claudia A.

In: Scientific Reports, Vol. 8, No. 1, 8646, 05.06.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein

AU - Martin, Esther M.

AU - Kondrat, Frances D.L.

AU - Stewart, Alan J.

AU - Scrivens, James H.

AU - Sadler, Peter J.

AU - Blindauer, Claudia A.

PY - 2018/6/5

Y1 - 2018/6/5

N2 - Zinc modulates the biological function of histidine-rich glycoprotein (HRG) through binding to its His-rich region (HRR). The Zn2+-binding properties of a 35 amino-acid biologically-active peptide mimic of the HRR, HRGP330, were investigated using dissociative mass spectrometry approaches in addition to travelling-wave ion mobility mass spectrometry (TWIM-MS). Native mass spectrometry confirmed zinc binding to HRGP330; however, broadening of the 1H NMR resonances upon addition of Zn2+ ions precluded the attainment of structural information. A complementary approach employing TWIM-MS indicated that HRGP330 has a more compact structure in the presence of Zn2+ ions. Top-down MS/MS data supported a metal-binding-induced conformational change, as fewer fragments were observed for Zn2+-bound HRGP330. Zn2+-bound fragments of both N-terminal and C-terminal ends of the peptide were identified from collision-induced dissociation (CID) and electron transfer dissociation/proton transfer reaction (ETD/PTR) experiments, suggesting that multiple binding sites exist within this region of HRG. The combination of mass spectrometry and NMR approaches provides new insight into the highly dynamic interaction between zinc and this His-rich peptide.

AB - Zinc modulates the biological function of histidine-rich glycoprotein (HRG) through binding to its His-rich region (HRR). The Zn2+-binding properties of a 35 amino-acid biologically-active peptide mimic of the HRR, HRGP330, were investigated using dissociative mass spectrometry approaches in addition to travelling-wave ion mobility mass spectrometry (TWIM-MS). Native mass spectrometry confirmed zinc binding to HRGP330; however, broadening of the 1H NMR resonances upon addition of Zn2+ ions precluded the attainment of structural information. A complementary approach employing TWIM-MS indicated that HRGP330 has a more compact structure in the presence of Zn2+ ions. Top-down MS/MS data supported a metal-binding-induced conformational change, as fewer fragments were observed for Zn2+-bound HRGP330. Zn2+-bound fragments of both N-terminal and C-terminal ends of the peptide were identified from collision-induced dissociation (CID) and electron transfer dissociation/proton transfer reaction (ETD/PTR) experiments, suggesting that multiple binding sites exist within this region of HRG. The combination of mass spectrometry and NMR approaches provides new insight into the highly dynamic interaction between zinc and this His-rich peptide.

UR - http://www.scopus.com/inward/record.url?scp=85048117046&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-26924-1

DO - 10.1038/s41598-018-26924-1

M3 - Article

VL - 8

JO - Nature Scientific Reports

JF - Nature Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8646

ER -