Preferential Protein Partitioning in Biological Membrane with Coexisting Liquid Ordered and Liquid Disordered Phase Beha
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Preferential Protein Partitioning in Biological Membrane with Coexisting Liquid Ordered and Liquid Disordered Phase Behavior: Underlying Design Principles Jessica Bodosa1 · Sahithya S. Iyer1 · Anand Srivastava1 Received: 14 September 2020 / Accepted: 31 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Several studies now show that certain proteins exhibit selective preference toward liquid ordered (Lo ) or toward liquid disordered (Ld ) regions of the heterogeneous membrane and some of them have preference for the L o-Ld interface. Spatially heterogenous organization of lipids, enriched in specific protein molecules, function as platforms for signaling and are involved in several other physiologically critical functions. In this review, we collate together some of the experimental observations of cases where proteins preferentially segregate into different phases and highlight the importance of these preferential localization in terms of underlying functions. We also try to understand the structural features and chemical makeup of the membrane-interacting motifs of these proteins. Finally, we put forth some preliminary analysis on class I viral fusion proteins, some of which are known to partition at the L o-Ld interface, and through them we try to understand the evolutionary design principles of phase segregating proteins. Put together, this review summarizes the existing studies on preferential partitioning of proteins into different membrane phases while emphasizing the need to understand the molecular design-level features that can help us “engineer” functionally rich peptides and proteins with a programmed membrane partitioning. Graphic Abstract
Keywords Lipid nanodomain · Liquid–liquid phase separation in membrane · Preferential protein partitioning · Viral fusion peptides
Introduction
* Anand Srivastava [email protected] 1
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka 560012, India
About 150 years ago, Charles Ernest Overton along with Hans Horst Meyer, while trying to understand the movement of anesthesia and other solutes between the environment and the interior of living cells, established the concept of semipermeable nature of cell boundaries while also suggesting
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that the boundary layer is composed of ”aliphatic” lipid molecules. Presumably, this laid the foundation of biological membrane science (Perouansky 2015; Kleinzeller et al. 1999). Of course, 150 years later, we now know that role of biological membrane transcends far beyond that of a semi-permeable boundary. From recent lipidomics data, it is established that there are more that 40,000 chemically different known lipid types in Eukaryotic cells and the plasma membrane itself has more than 800 different types of lipids (Dowhan 2017; Yang and Han 2016; Shevchenko and Simons 2010; Brügger 2014; Barrera et al. 2013; Levental et al. 2016; Stone et al. 2017; van Meer and de Kroon 2011; Iyer and Srivastava 2020). Differential molecular interac
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