The role of proline residues in the dynamics of transmembrane helices: the case of bacteriorhodopsin

Perálvarez-Marín, Àlex; Bourdelande, José-Luis; Querol, Enric; Padrós, Esteve

doi:10.1080/09687860500435019

Cited by 16 publications

(26 citation statements)

References 39 publications

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“…the S6 helix of Kv channels [56], a more systematic and comparative computational analysis of all such helices from a given membrane transport protein has, to the best of our knowledge, yet to be published. Furthermore, a number of experimental studies have recently addressed the structural [57] and functional [58] consequences of proline-to-alanine mutations in bacteriorhodopsin, the latter study suggesting a functionally relevant dynamic role for helix kinks. Thus, in the current study we have presented one of the first comparisons of single TM helix simulations with simulations of an intact membrane transport protein.…”

Section: Discussionmentioning

confidence: 99%

Helix dynamics in a membrane transport protein: comparative simulations of the glycerol-3-phosphate transporter and its constituent helices

D'Rozario

Sansom

2008

Molecular Membrane Biology

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The glycerol-3-phosphate transporter (GlpT) is a member of the major facilitator superfamily (MFS). GlpT is an organic phosphate/inorganic phosphate antiporter. It shares a similar fold with other MFS transporters (e.g. LacY and EmrD) consisting of 12 transmembrane (TM) helices which form two domains (each of six TM helices) surrounding a central ligand-binding cavity. The TM helices (especially the cavity-lining helices) contain a large number of proline and glycine residues, which may aid in the conformational changes believed to underline the transport mechanism. Molecular dynamics simulations in a phospholipid bilayer have been used to compare the conformational properties of the isolated TM helices with those in the intact GlpT protein. Analysis of these simulations focuses on the role of proline-induced flexibility in the TM helices. Our results are consistent with the proposed rocker switch mechanism for transport by GlpT. In particular, the simulations highlight the cavity-lining helices (H4, H5, H10 and H11) as being significantly flexible, suggesting that the transport mechanism may involve intra-helix motions in addition to pseudo-rigid body motions of the N- and C-terminal domains relative to one another.

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Section: Discussionmentioning

confidence: 99%

Helix dynamics in a membrane transport protein: comparative simulations of the glycerol-3-phosphate transporter and its constituent helices

D'Rozario

Sansom

2008

Molecular Membrane Biology

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“…Mutation of Thr90 leads to a severely affected proton transport function. 3,4 Another strong inter-helical interaction is present between helices C and D through Leu87 and Asp115 (via a water molecule). Through these interactions, Asp115 in helix D participates decisively in modulation of helix C dynamics, since the interactions performed are designed to drive properly the cytoplasmic events of the photocycle, where Asp96 is the main residue involved.…”

Section: Signal Transduction and The Dynamics Of Helices C And Dmentioning

confidence: 99%

“…2 In the same helix C, at the level of the SB (between Asp85 and Asp96) we find the presence of a dynamic motif Thr90-Pro91 which seems to be in charge of synchronizing the proton transfer steps with the protein conformational changes, leading to optimal proton pumping activity. [3][4][5] In helix D, at the level of the SB and oriented toward the Thr90-Pro91 motif, we find Asp115. It is a high conserved residue among microbial rhodopsins 6,7 and its role, although still unclear, is supposed to be relevant.…”

Section: Introductionmentioning

confidence: 97%

Inter-helical Hydrogen Bonds Are Essential Elements for Intra-protein Signal Transduction: The Role of Asp115 in Bacteriorhodopsin Transport Function

Perálvarez-Marín

Lórenz-Fonfrı́a

Bourdelande

et al. 2007

Journal of Molecular Biology

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“…Tables Table 1. Comparison of natural variation and introduced mutations in retinal-binding pocket of GR and homologs. E [53] N [53] V [54] S [54] T [55] F [56] A [57] D [58] N [59] V [60] A [61] V [61] A [62] T [62] V [62] A [26] -C [63] -C [60] A [26] C [57] V [57] A [63] F [56] F [64] A [65] L [66] V [60] F [67] E [68] N [26] T [26] - G [25] A [25] A [25] K [70] ---------H [25] N [25] --E [71] --a Homologous residues in the retinal-binding pocket were identified through structure-guided alignment of protein sequences. b Natural variation represents variants retrieved from BLAST searches of the NCBI database with GR, BR and PR.…”

Section: Figurementioning

confidence: 99%

Directed Evolution of Gloeobacter violaceus Rhodopsin Spectral Properties

Engqvist

McIsaac

Dollinger

et al. 2015

Journal of Molecular Biology

124

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Proton-pumping rhodopsins (PPRs) are photoactive retinal-binding proteins that transport ions across biological membranes in response to light. These proteins are interesting for lightharvesting applications in bioenergy production, in optogenetics applications in neuroscience, and as fluorescent sensors of membrane potential. Little is known, however, about how the protein sequence determines the considerable variation in spectral properties of PPRs from different biological niches or how to engineer these properties in a given PPR. Here we report a comprehensive study of amino acid substitutions in the retinal binding pocket of Gloeobacter violacaeus rhodopsin (GR) that tune its spectral properties. Directed evolution generated 70 GR variants with absorption maxima shifted by up to +/-80 nm, extending the protein's light absorption significantly beyond the range of known natural PPRs. While proton pumping activity was disrupted in many of the spectrally shifted variants, we identified single tuning mutations that incurrred blue and red shifts of 42 nm and 22 nm, respectively, that did not disrupt proton pumping. Blue-shifting mutations were distributed evenly along the retinal molecule while redshifting mutations were clustered near the residue K257, which forms a covalent bond with retinal through a Schiff base linkage. Thirty-four of the identified tuning mutations are not found in known microbial rhodopsins. We discovered a subset of red-shifted GRs that exhibit high levels of fluorescence relative to the wild-type protein.

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The role of proline residues in the dynamics of transmembrane helices: the case of bacteriorhodopsin

Cited by 16 publications

References 39 publications

Helix dynamics in a membrane transport protein: comparative simulations of the glycerol-3-phosphate transporter and its constituent helices

Helix dynamics in a membrane transport protein: comparative simulations of the glycerol-3-phosphate transporter and its constituent helices

Inter-helical Hydrogen Bonds Are Essential Elements for Intra-protein Signal Transduction: The Role of Asp115 in Bacteriorhodopsin Transport Function

Directed Evolution of Gloeobacter violaceus Rhodopsin Spectral Properties

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