Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.

Fluorescent proteins that can switch between distinct colors have contributed significantly to modern biomedical imaging technologies and molecular cell biology. Here we report the identification and biochemical analysis of a green-shifted red fluorescent protein variant GmKate, produced by the intr...

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Main Authors: Qi Wang, Laura J Byrnes, Bo Shui, Ute F Röhrig, Avtar Singh, Dmitriy M Chudakov, Sergey Lukyanov, Warren R Zipfel, Michael I Kotlikoff, Holger Sondermann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023513&type=printable
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author Qi Wang
Laura J Byrnes
Bo Shui
Ute F Röhrig
Avtar Singh
Dmitriy M Chudakov
Sergey Lukyanov
Warren R Zipfel
Michael I Kotlikoff
Holger Sondermann
author_facet Qi Wang
Laura J Byrnes
Bo Shui
Ute F Röhrig
Avtar Singh
Dmitriy M Chudakov
Sergey Lukyanov
Warren R Zipfel
Michael I Kotlikoff
Holger Sondermann
author_sort Qi Wang
collection DOAJ
description Fluorescent proteins that can switch between distinct colors have contributed significantly to modern biomedical imaging technologies and molecular cell biology. Here we report the identification and biochemical analysis of a green-shifted red fluorescent protein variant GmKate, produced by the introduction of two mutations into mKate. Although the mutations decrease the overall brightness of the protein, GmKate is subject to pH-dependent, reversible green-to-red color conversion. At physiological pH, GmKate absorbs blue light (445 nm) and emits green fluorescence (525 nm). At pH above 9.0, GmKate absorbs 598 nm light and emits 646 nm, far-red fluorescence, similar to its sequence homolog mNeptune. Based on optical spectra and crystal structures of GmKate in its green and red states, the reversible color transition is attributed to the different protonation states of the cis-chromophore, an interpretation that was confirmed by quantum chemical calculations. Crystal structures reveal potential hydrogen bond networks around the chromophore that may facilitate the protonation switch, and indicate a molecular basis for the unusual bathochromic shift observed at high pH. This study provides mechanistic insights into the color tuning of mKate variants, which may aid the development of green-to-red color-convertible fluorescent sensors, and suggests GmKate as a prototype of genetically encoded pH sensors for biological studies.
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spelling doaj-art-eaf6abd054c74006af0981c4e88e0a132025-08-20T02:30:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2351310.1371/journal.pone.0023513Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.Qi WangLaura J ByrnesBo ShuiUte F RöhrigAvtar SinghDmitriy M ChudakovSergey LukyanovWarren R ZipfelMichael I KotlikoffHolger SondermannFluorescent proteins that can switch between distinct colors have contributed significantly to modern biomedical imaging technologies and molecular cell biology. Here we report the identification and biochemical analysis of a green-shifted red fluorescent protein variant GmKate, produced by the introduction of two mutations into mKate. Although the mutations decrease the overall brightness of the protein, GmKate is subject to pH-dependent, reversible green-to-red color conversion. At physiological pH, GmKate absorbs blue light (445 nm) and emits green fluorescence (525 nm). At pH above 9.0, GmKate absorbs 598 nm light and emits 646 nm, far-red fluorescence, similar to its sequence homolog mNeptune. Based on optical spectra and crystal structures of GmKate in its green and red states, the reversible color transition is attributed to the different protonation states of the cis-chromophore, an interpretation that was confirmed by quantum chemical calculations. Crystal structures reveal potential hydrogen bond networks around the chromophore that may facilitate the protonation switch, and indicate a molecular basis for the unusual bathochromic shift observed at high pH. This study provides mechanistic insights into the color tuning of mKate variants, which may aid the development of green-to-red color-convertible fluorescent sensors, and suggests GmKate as a prototype of genetically encoded pH sensors for biological studies.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023513&type=printable
spellingShingle Qi Wang
Laura J Byrnes
Bo Shui
Ute F Röhrig
Avtar Singh
Dmitriy M Chudakov
Sergey Lukyanov
Warren R Zipfel
Michael I Kotlikoff
Holger Sondermann
Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.
PLoS ONE
title Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.
title_full Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.
title_fullStr Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.
title_full_unstemmed Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.
title_short Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein mKate variant.
title_sort molecular mechanism of a green shifted ph dependent red fluorescent protein mkate variant
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0023513&type=printable
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