Exploring gas permeability of cellular membranes and membrane channels with molecular dynamics

Wang, Yi; Cohen, Joseph R.; Boron, Walter F.; Schulten, Klaus; Tajkhorshid, Emad

doi:10.1016/j.jsb.2006.11.008

Cited by 182 publications

(222 citation statements)

References 68 publications

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“…Crystallographic data show that xenon can enter the central pore of the bacterial Rh50 (21). Moreover, in the case of AQP1, molecular-dynamics simulations show that CO 2 could penetrate the 4 aquapores or, with greater ease, the central pore (7). We hypothesize that the CO 2 /NH 3 selectivities that we observe reflect the relative permeabilities of the 2 gases through the monomeric vs. the central pores of the 5 channels we studied.…”

Section: Discussionmentioning

confidence: 67%

“…Endeward et al (6) demonstrated that AQP1 accounts for Ϸ60% of the CO 2 permeability of human red blood cells (RBCs). Molecular dynamics simulations suggest that CO 2 can pass through the 4 aquapores of an AQP1 tetramer (7) and especially through the central pore between the 4 monomers (7). Additional data indicate that AQP1 is permeable to nitric oxide (8), and that-when expressed in Xenopus oocytes (9,10) or when reconstituted into planar lipid bilayers (11)-AQP1, AQP3, AQP8, AQP9, and the plant aquaporin TIP2;1 are all permeable to NH 3 .…”

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confidence: 99%

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Relative CO ₂ /NH ₃ selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Musa‐Aziz

Chen

Pelletier

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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238

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The water channel aquaporin 1 (AQP1) and certain Rh-family members are permeable to CO 2 and NH3. Here, we use changes in surface pH (pH S) to assess relative CO2 vs. NH3 permeability of Xenopus oocytes expressing members of the AQP or Rh family. Exposed to CO 2 or NH3, AQP1 oocytes exhibit a greater maximal magnitude of pH S change (⌬pHS) compared with day-matched controls injected with H 2O or with RNA encoding SGLT1, NKCC2, or PepT1. With CO 2, AQP1 oocytes also have faster time constants for pH S relaxation ( pHs). Thus, AQP1, but not the other proteins, conduct CO 2 and NH3. Oocytes expressing rat AQP4, rat AQP5, human RhAG, or the bacterial Rh homolog AmtB also exhibit greater ⌬pH S(CO2) and faster pHs compared with controls. Oocytes expressing AmtB and RhAG, but not AQP4 or AQP5, exhibit greater ⌬pH S(NH3) values. Only AQPs exhibited significant osmotic water permeability (P f). We computed channel-dependent (*) ⌬pHS or Pf by subtracting values for H2O oocytes from those of channelexpressing oocytes. For the ratio ⌬pH S(CO2)*/Pf ‫ء‬ , the sequence was AQP5 > AQP1 Х AQP4. For ⌬pH S(CO2)*/⌬pHS(NH3)*, the sequence was AQP4 Х AQP5 > AQP1 > AmtB > RhAG. Thus, each channel exhibits a characteristic ratio for indices of CO 2 vs. NH3 permeability, demonstrating that, like ion channels, gas channels can exhibit selectivity.gas channel ͉ oocyte ͉ permeability ͉ signal peptide ͉ surface pH measurement G as transport through membranes is of fundamental importance for nutritive transport, photosynthesis, oxidative metabolism, and signaling. For most of the past century, we assumed that gas molecules cross biological membranes merely by diffusing through the lipid phase. This dogma was challenged by 2 observations: (i) Apical membranes of gastric-gland cells have no demonstrable permeability to CO 2 or NH 3 (1). (ii) Heterologous expression of the water channel aquaporin 1 (AQP1) increases the CO 2 permeability of Xenopus oocytes (2). Cooper and Boron (3) and Prasad et al. (4) confirmed and extended this observation. Uehlein (5) showed that an AQP plays a physiological role by enhancing CO 2 uptake by plants. Endeward et al. (6) demonstrated that AQP1 accounts for Ϸ60% of the CO 2 permeability of human red blood cells (RBCs). Molecular dynamics simulations suggest that CO 2 can pass through the 4 aquapores of an AQP1 tetramer (7) and especially through the central pore between the 4 monomers (7). Additional data indicate that AQP1 is permeable to nitric oxide (8), and that-when expressed in Xenopus oocytes (9, 10) or when reconstituted into planar lipid bilayers (11)-AQP1, AQP3, AQP8, AQP9, and the plant aquaporin TIP2;1 are all permeable to NH 3 .The AmtB/MEP/Rh proteins represent a second family of gas channels (12-15). Early work showed that AmtB and MEP transport NH 3 or NH 4 ϩ , thereby playing a nutritive role in archaea, bacteria, and fungi (16,17). The crystal structures of the bacterial AmtB (18-20) and Rh50 (21) and the fungal Amt-1 (22) are consistent with the idea that NH 3 passes through a pore in each m...

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Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 99%

Relative CO ₂ /NH ₃ selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Musa‐Aziz

Chen

Pelletier

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

238

244

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“…More recently, Wang et al corroborated this picture (Wang et al 2007) and showed that it holds qualitatively also to molecular oxygen. Like CO 2 , also O 2 might permeate through the apolar central cavity.…”

Section: Are Aquaporins Permeated By Gas?mentioning

confidence: 73%

Dynamics and Energetics of Permeation Through Aquaporins. What Do We Learn from Molecular Dynamics Simulations?

Hub

Grubmüller

Groot

2009

Handbook of Experimental Pharmacology

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“…25 Recent developments in efficient computational sampling methods have allowed thorough scanning of the possible pathways for gas diffusion in the interior of proteins. [26][27][28][29] For example, such computational investigations have proved useful in understanding gas diffusion in many protein systems such as molecular dioxygen pathways via dynamic oxygen access channels in flavoproteins, [30][31][32] ammonia transport in carbamoyl phosphate synthetase, [33][34][35] and gas diffusion and channeling in hemoglobin. 28,36 In this paper, we use explicit solvent all-atom molecular dynamics (MD) simulations to investigate the protein barrel fluctuations in mCherry, which is one of the most useful monomeric variants of RFP.…”

Section: Introductionmentioning

confidence: 99%

Fluorescent protein barrel fluctuations and oxygen diffusion pathways in mCherry

Chapagain

Regmi

Castillo

2011

The Journal of Chemical Physics

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Fluorescent proteins (FPs) are valuable tools as biochemical markers for studying cellular processes. Red fluorescent proteins (RFPs) are highly desirable for in vivo applications because they absorb and emit light in the red region of the spectrum where cellular autofluorescence is low. The naturally occurring fluorescent proteins with emission peaks in this region of the spectrum occur in dimeric or tetrameric forms. The development of mutant monomeric variants of RFPs has resulted in several novel FPs known as mFruits. Though oxygen is required for maturation of the chromophore, it is known that photobleaching of FPs is oxygen sensitive, and oxygen-free conditions result in improved photostabilities. Therefore, understanding oxygen diffusion pathways in FPs is important for both photostabilites and maturation of the chromophores. In this paper, we use molecular dynamics calculations to investigate the protein barrel fluctuations in mCherry, which is one of the most useful monomeric mFruit variant. We employ implicit ligand sampling to determine oxygen pathways from the bulk solvent into the mCherry chromophore in the interior of the protein. We also show that these pathways can be blocked or altered and barrel fluctuations can be reduced by strategic amino acid substitutions.

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Exploring gas permeability of cellular membranes and membrane channels with molecular dynamics

Cited by 182 publications

References 68 publications

Relative CO ₂ /NH ₃ selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Relative CO ₂ /NH ₃ selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Dynamics and Energetics of Permeation Through Aquaporins. What Do We Learn from Molecular Dynamics Simulations?

Fluorescent protein barrel fluctuations and oxygen diffusion pathways in mCherry

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Exploring gas permeability of cellular membranes and membrane channels with molecular dynamics

Cited by 182 publications

References 68 publications

Relative CO 2 /NH 3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Relative CO 2 /NH 3 selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Dynamics and Energetics of Permeation Through Aquaporins. What Do We Learn from Molecular Dynamics Simulations?

Fluorescent protein barrel fluctuations and oxygen diffusion pathways in mCherry

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Product

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Relative CO ₂ /NH ₃ selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG

Relative CO ₂ /NH ₃ selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG