Membrane proteins and proteomics: Love is possible, but so difficult

TL;DR

This paper reviews the challenges in membrane protein proteomics, highlighting the difficulties in solubilization, the shift towards alternative separation methods, and the impact on mass spectrometry analysis.

Contribution

It critically examines the evolution of membrane proteomics methods, emphasizing the shift from traditional electrophoresis to alternative approaches due to solubility issues.

Findings

Membrane proteins are difficult to analyze due to solubility challenges.

Alternative methods to 2D electrophoresis are increasingly used in membrane proteomics.

In some cases, 2D electrophoresis remains effective for membrane protein analysis.

Abstract

Despite decades of extensive research, the large-scale analysis of membrane proteins remains a difficult task. This is due to the fact that membrane proteins require a carefully balanced hydrophilic and lipophilic environment, which optimum varies with different proteins, while most protein chemistry methods work mainly, if not only, in water-based media. Taking this review [Santoni, Molloy and Rabilloud, Membrane proteins and proteomics: un amour impossible? Electrophoresis 2000, 21, 1054-1070] as a pivotal paper, the current paper analyzes how the field of membrane proteomics exacerbated the trend in proteomics, i.e. developing alternate methods to the historical two-dimensional electrophoresis, and thus putting more and more pressure on the mass spectrometry side. However, in the case of membrane proteins, the incentive in doing so is due to the poor solubility of membrane proteins. This review also shows that in some situations, where this solubility problem is less acute, two-dimensional electrophoresis remains a method of choice. Last but not least, this review also critically examines the alternate approaches that have been used for the proteomic analysis of membrane proteins.