Does arginine remain protonated in the lipid membrane? Insights from microscopic pKa calculations

Biophysical Journal
Jejoong Yoo, Qiang Cui

Abstract

Free energy perturbation calculations are carried out to estimate the effective pK(a) of an arginine (Arg) sidechain as a function of its location in the dipalmitoylphosphatidylcholine bilayer. Similar to previous all-atom simulations of the voltage sensor domain of a potassium channel in the membrane with charged Arg residues, the membrane and water structures deform to stabilize the charge of the Arg analog. As a result, the computed pK(a) is >7 throughout the membrane although the value is very close to 7 near the center of the bilayer. With additional stabilizations from negatively charged amino acids or lipid molecules, it is reasonable to expect that Arg in membrane proteins (once in the membrane) can adopt the protonated state despite the low dielectric nature of the bulk lipid membrane.

References

Aug 1, 1986·Journal of Biochemical and Biophysical Methods·M B Djamgoz, J Dawson
May 2, 2003·Nature·Youxing JiangRoderick MacKinnon
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Oct 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·J Alfredo FreitesStephen H White
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·S M Fuchs, R T Raines
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Peter J Bond, Mark S P Sansom
Apr 18, 2007·The Journal of General Physiology·Justin L MacCallumD Peter Tieleman
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus

❮ Previous
Next ❯

Citations

Mar 3, 2010·Journal of Molecular Modeling·Siti Azma JusohVolkhard Helms
Oct 6, 2012·Chemical Reviews·Christopher MaffeoAleksei Aksimentiev
Nov 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael J HarmsBertrand García-Moreno
May 15, 2013·FEBS Letters·Chérine Bechara, Sandrine Sagan
Nov 5, 2015·Proteins·Igor VorobyovArieh Warshel
Mar 24, 2009·Trends in Biochemical Sciences·Armen Y MulkidjanianEugene V Koonin
Mar 27, 2015·Protein Science : a Publication of the Protein Society·Carolyn A FitchLawrence P McIntosh
Jan 20, 2011·Biophysical Journal·Chze Ling WeeMark S P Sansom
Jan 13, 2011·Biochimica Et Biophysica Acta·Siti Azma Jusoh, Volkhard Helms
Nov 10, 2009·Biochimica Et Biophysica Acta·Ana BouchetE Aníbal Disalvo
Jun 30, 2015·Structure·Frank V MarcolineMichael Grabe
May 9, 2015·Biophysical Journal·Pedro R MagalhãesAntónio M Baptista
Feb 21, 2016·Biochimica Et Biophysica Acta·James C Gumbart, Christophe Chipot
Feb 13, 2016·The FEBS Journal·Gustavo ChavesBoris Musset
Jan 15, 2014·Journal of Magnetic Resonance·Timothy A CrossAnna Wright
Jan 21, 2014·Journal of Molecular Graphics & Modelling·Brad Van OostenThad A Harroun
Jan 27, 2009·Biophysical Journal·Sascha TayefehStefan M Kast
Jul 5, 2011·Biophysical Journal·Justin L MacCallumD Peter Tieleman
Aug 3, 2012·Biophysical Journal·P WadhwaniR M Epand
Nov 10, 2010·Journal of Molecular Biology·Michael S ChimentiBertrand García-Moreno E
Feb 24, 2017·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Bo XuMusahid Ahmed
Feb 6, 2017·Biochimica Et Biophysica Acta. Biomembranes·Xiaochao ChenJeremy Bradshaw
Mar 17, 2018·International Journal of Molecular Sciences·Zanxia CaoYaoqi Zhou
Mar 26, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Satoshi OhtakeA Hajime Koyama
Oct 14, 2010·Molecular Membrane Biology·Oleg A AndreevYana K Reshetnyak
Feb 2, 2016·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Zhen-lu LiYu-qiang Ma
Nov 6, 2015·Protein Science : a Publication of the Protein Society·Marina EvichMarkus W Germann
Nov 24, 2017·Chemical Communications : Chem Comm·Munesh Kumar HarioudhJimut Kanti Ghosh
Jul 22, 2016·The Journal of Biological Chemistry·Ashley N MartfeldRoger E Koeppe

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.