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Journal article

A robust mass spectrometry method for rapid profiling of erythrocyte ghost membrane proteomes

Abstract:

Background

Red blood cell (RBC) physiology is directly linked to many human disorders associated with low tissue oxygen levels or anemia including chronic obstructive pulmonary disease, congenital heart disease, sleep apnea and sickle cell anemia. Parasites such as Plasmodium spp. and phylum Apicomplexa directly target RBCs, and surface molecules within the RBC membrane are critical for pathogen interactions. Proteomics of RBC membrane ‘ghost’ fractions has therefore been of considerable interest, but protocols described to date are either suboptimal or too extensive to be applicable to a larger set of clinical cohorts.

Methods

Here, we describe an optimised erythrocyte isolation protocol from blood, tested for various storage conditions and explored using different fractionation conditions for isolating ghost RBC membranes. Liquid chromatography mass spectrometry (LC–MS) analysis on a Q-Exactive Orbitrap instrument was used to profile proteins isolated from the comparative conditions. Data analysis was run on the MASCOT and MaxQuant platforms to assess their scope and diversity.

Results

The results obtained demonstrate a robust method for membrane enrichment enabling consistent MS based characterisation of > 900 RBC membrane proteins in single LC–MS/MS analyses. Non-detergent based membrane solubilisation methods using the tissue and supernatant fractions of isolated ghost membranes are shown to offer effective haemoglobin removal as well as diverse recovery including erythrocyte membrane proteins of high and low abundance.

Conclusions

The methods described in this manuscript propose a medium to high throughput framework for membrane proteome profiling by LC–MS of potential applicability to larger clinical cohorts in a variety of disease contexts.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1186/s12014-018-9190-4

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; NDM Experimental Medicine
Role:
Author


Publisher:
BioMed Central
Journal:
Clinical Proteomics More from this journal
Volume:
15
Pages:
14
Publication date:
2018-03-21
Acceptance date:
2018-03-13
DOI:
EISSN:
1559-0275
ISSN:
1542-6416


Keywords:
Pubs id:
pubs:831971
UUID:
uuid:6ae9d8cf-4e06-482a-bd93-730a765f3706
Local pid:
pubs:831971
Source identifiers:
831971
Deposit date:
2018-04-04

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