scholarly journals Modulation of Function, Structure and Clustering of K+ Channels by Lipids: Lessons Learnt from KcsA

2020 ◽  
Vol 21 (7) ◽  
pp. 2554 ◽  
Author(s):  
María Lourdes Renart ◽  
Ana Marcela Giudici ◽  
Clara Díaz-García ◽  
María Luisa Molina ◽  
Andrés Morales ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Experimental System ◽  
Integral Membrane Protein ◽  
Lipid Binding ◽  
Common Element ◽  
Protein Protein Interactions ◽  
Expression And Purification ◽  
Arginine Residues ◽  
Channel Currents ◽  
Specific Lipid

KcsA, a prokaryote tetrameric potassium channel, was the first ion channel ever to be structurally solved at high resolution. This, along with the ease of its expression and purification, made KcsA an experimental system of choice to study structure–function relationships in ion channels. In fact, much of our current understanding on how the different channel families operate arises from earlier KcsA information. Being an integral membrane protein, KcsA is also an excellent model to study how lipid–protein and protein–protein interactions within membranes, modulate its activity and structure. In regard to the later, a variety of equilibrium and non-equilibrium methods have been used in a truly multidisciplinary effort to study the effects of lipids on the KcsA channel. Remarkably, both experimental and “in silico” data point to the relevance of specific lipid binding to two key arginine residues. These residues are at non-annular lipid binding sites on the protein and act as a common element to trigger many of the lipid effects on this channel. Thus, processes as different as the inactivation of channel currents or the assembly of clusters from individual KcsA channels, depend upon such lipid binding.

scholarly journals Allostery revealed within lipid binding events to membrane proteins

2018 ◽  
Vol 115 (12) ◽  
pp. 2976-2981 ◽  
Author(s):  
John W. Patrick ◽  
Christopher D. Boone ◽  
Wen Liu ◽  
Gloria M. Conover ◽  
Yang Liu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Biological Membrane ◽  
Binding Constants ◽  
Native Mass Spectrometry ◽  
Specific Protein ◽  
Lipid Binding ◽  
Allosteric Modulation ◽  
Lipid Species ◽  
Specific Lipid

Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein−lipid assemblies. Despite this inherent complexity, the identification of specific protein−lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery [Monod J, Wyman J, Changeux JP (1965)J Mol Biol12:88–118]. Here, we use native mass spectrometry to determine the allosteric nature of heterogeneous lipid binding events to membrane proteins. We monitored individual lipid binding events to the ammonia channel (AmtB) fromEscherichia coli, enabling determination of their equilibrium binding constants. We found that different lipid pairs display a range of allosteric modulation. In particular, the binding of phosphatidylethanolamine and cardiolipin-like molecules to AmtB exhibited the largest degree of allosteric modulation, inspiring us to determine the cocrystal structure of AmtB in this lipid environment. The 2.45-Å resolution structure reveals a cardiolipin-like molecule bound to each subunit of the trimeric complex. Mutation of a single residue in AmtB abolishes the positive allosteric modulation observed for binding phosphatidylethanolamine and cardiolipin-like molecules. Our results demonstrate that specific lipid−protein interactions can act as allosteric modulators for the binding of different lipid types to integral membrane proteins.

Molecular simulations and lipid–protein interactions: potassium channels and other membrane proteins

2005 ◽  
Vol 33 (5) ◽  
pp. 916-920 ◽  
Author(s):  
M.S.P. Sansom ◽  
P.J. Bond ◽  
S.S. Deol ◽  
A. Grottesi ◽  
S. Haider ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Binding Site ◽  
Protein Interactions ◽  
Outer Membrane Proteins ◽  
Lipid Binding ◽  
Potassium Channel Kcsa ◽  
Head Groups ◽  
Arginine Residues ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations

Molecular dynamics simulations may be used to probe the interactions of membrane proteins with lipids and with detergents at atomic resolution. Examples of such simulations for ion channels and for bacterial outer membrane proteins are described. Comparison of simulations of KcsA (an α-helical bundle) and OmpA (a β-barrel) reveals the importance of two classes of side chains in stabilizing interactions with the head groups of lipid molecules: (i) tryptophan and tyrosine; and (ii) arginine and lysine. Arginine residues interacting with lipid phosphate groups play an important role in stabilizing the voltage-sensor domain of the KvAP channel within a bilayer. Simulations of the bacterial potassium channel KcsA reveal specific interactions of phosphatidylglycerol with an acidic lipid-binding site at the interface between adjacent protein monomers. A combination of molecular modelling and simulation reveals a potential phosphatidylinositol 4,5-bisphosphate-binding site on the surface of Kir6.2.

scholarly journals Use of G-protein fusions to monitor integral membrane protein–protein interactions in yeast

10.1038/80274 ◽  
2000 ◽  
Vol 18 (10) ◽  
pp. 1075-1079 ◽  
Author(s):  
Kathleen N. Ehrhard ◽  
Jörg J. Jacoby ◽  
Xin-Yuan Fu ◽  
Reinhard Jahn ◽  
Henrik G. Dohlman
Keyword(s):  
Membrane Protein ◽  
G Protein ◽  
Protein Interactions ◽  
Integral Membrane Protein ◽  
Protein Protein Interactions

Rh50 Glycoprotein Gene and Rhnull Disease: A Silent Splice Donor Is trans to a Gly279→Glu Missense Mutation in the Conserved Transmembrane Segment

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1776-1784 ◽  
Author(s):  
Cheng-Han Huang ◽  
Zhi Liu ◽  
Guangjie Cheng ◽  
Ying Chen
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Integral Membrane Protein ◽  
Gene Organization ◽  
Comparative Genomic ◽  
Transmembrane Segment ◽  
Protein Protein Interactions ◽  
Genomic Studies ◽  
American Society ◽  
Gt Element

Abstract Rhnull disease includes the amorph and regulator types that are thought to result from homozygous mutations at theRH30 and RH50 loci, respectively. Here we report an unusual regulator Rhnull where two G→A nucleotide (nt) transitions occurred in trans, targeting different regions of the two copies of Rh50 gene. The nt 836 G→A mutation was a missense change located in exon 6; it converted Gly into Glu at position 279, a central amino acid of the transmembrane segment 9 (TM9). While cDNA analysis showed expression of the 836A(Glu279) allele only, genomic studies showed the presence of both 836A(Glu279) and 836G(Gly279) alleles. A detailed analysis of gene organization led to the identification in the Rh50(836G) allele of a defective donor splice site, caused by a G→A mutation in the invariant GT element of intron 1. This is the first known example of such mutations that has apparently abolished the functional splicing of a pre-mRNA encoding a multipass integral membrane protein. With a silent phenotypic copy intrans, the negatively charged Glu279 residue may disrupt TM9 and impair the interaction of the missense protein with Rh30 polypeptides. To evaluate the significance of the mutation, we took a comparative genomic approach and identified Rh50 homologues in different species. We found that Gly279 is a conserved residue and its adjacent amino acid sequence is identical fromCaenorhabditis elegans to human. These findings provide new insight into the diversity of Rhnull disease and suggest that the C-terminal region of Rh50 may also participate in protein-protein interactions involving Rh complex formation. © 1998 by The American Society of Hematology.

Lipid–Protein Interactions in Plasma Membrane Organization and Function

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Taras Sych ◽  
Kandice R. Levental ◽  
Erdinc Sezgin
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Collective Behavior ◽  
Protein Function ◽  
Lipid Binding ◽  
Publication Date ◽  
Membrane Organization ◽  
Lipid Protein Interactions ◽  
And Function ◽  
Specific Lipid

Lipid–protein interactions in cells are involved in various biological processes, including metabolism, trafficking, signaling, host–pathogen interactions, and transmembrane transport. At the plasma membrane, lipid–protein interactions play major roles in membrane organization and function. Several membrane proteins have motifs for specific lipid binding, which modulate protein conformation and consequent function. In addition to such specific lipid–protein interactions, protein function can be regulated by the dynamic, collective behavior of lipids in membranes. Emerging analytical, biochemical, and computational technologies allow us to study the influence of specific lipid–protein interactions, as well as the collective behavior of membranes on protein function. In this article, we review the recent literature on lipid–protein interactions with a specific focus on the current state-of-the-art technologies that enable novel insights into these interactions. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Ca2+-dependent Lipid Binding Domain of P120GAPMediates Protein-Protein Interactions with Ca2+-dependent Membrane-binding Proteinss

1996 ◽  
Vol 271 (40) ◽  
pp. 24333-24336 ◽  
Author(s):  
Alison J. Davis ◽  
Jonathan T. Butt ◽  
John H. Walker ◽  
Stephen E. Moss ◽  
Debra J. Gawler
Keyword(s):  
Protein Interactions ◽  
Membrane Binding ◽  
Lipid Binding ◽  
Binding Domain ◽  
Protein Protein Interactions

scholarly journals Allosteric modulation of protein-protein interactions by individual lipid binding events

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiao Cong ◽  
Yang Liu ◽  
Wen Liu ◽  
Xiaowen Liang ◽  
Arthur Laganowsky
Keyword(s):  
Protein Interactions ◽  
Lipid Binding ◽  
Allosteric Modulation ◽  
Protein Protein Interactions

scholarly journals Arginine Methylation of the ICP27 RGG Box Regulates the Functional Interactions of ICP27 with SRPK1 and Aly/REF during Herpes Simplex Virus 1 Infection

2009 ◽  
Vol 83 (17) ◽  
pp. 8970-8975 ◽  
Author(s):  
Stuart K. Souki ◽  
Rozanne M. Sandri-Goldin
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Protein Interactions ◽  
Arginine Methylation ◽  
Protein Protein Interactions ◽  
Herpes Simplex Virus 1 ◽  
Methylation Inhibitor ◽  
Arginine Residues ◽  
Regulate Protein ◽  
Simplex Virus

ABSTRACT The herpes simplex virus 1 protein ICP27 is methylated on arginine residues within an RGG box, and arginine methylation regulates ICP27 export to the cytoplasm. Arginine methylation can regulate protein-protein interactions; therefore, we examined the effect of hypomethylation on ICP27's interactions with cellular proteins SRPK1 and Aly/REF, which bind to ICP27 through the RGG box region. During infections with viral mutants containing lysine substitutions or the methylation inhibitor adenosine dialdehyde, the interaction of ICP27 with SRPK1 and Aly/REF was decreased, as determined by coimmunoprecipitation and colocalization studies, indicating that ICP27 RGG box methylation regulates interaction with these proteins.

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