The scaffold proteins of lignin biosynthetic cytochrome P450 enzymes
Abstract
Lignin is a complex and irregular biopolymer of cross-linked phenylpropanoid units in plant secondary cell walls. Its biosynthesis requires three endoplasmic reticulum (ER)-resident cytochrome P450 monooxygenases, C4H, C3'H and F5H, to establish the structural characteristics of its monomeric precursors. Those P450 enzymes were reported to associate with each other or potentially with other soluble monolignol biosynthetic enzymes to form enzyme complex or metabolone. However, molecular basis governing such enzyme or pathway organization remains elusive. Here we show that Arabidopsis membrane steroid binding proteins (MSBPs) serve as scaffold physically organizing monolignol P450 monooxygenases thereby regulating lignin biosynthetic process. We find that although C4H, C3'H and F5H are in spatial proximity to each other on ER membrane in vivo, they do not appear to directly interact with each other. Instead, two MSBP proteins physically interact with all three P450 enzymes and, moreover, MSBPs themselves associate as homo- and heteromers on the ER membrane, thereby organizing P450 clusters. Down-regulation of MSBPs does not affect the transcription levels of monolignol biosynthetic P450 genes but substantially impairs the stability and activity of the MSBP-interacting P450 enzymes and, consequently, the lignin deposition, the accumulation of soluble phenolics in monolignol branch but not in flavonoid pathway. Furthermore,more »
- Authors:
-
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Stony Brook Univ., Stony Brook, NY (United States)
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States); Energy Frontier Research Centers (EFRC) (United States). Center for Lignocellulose Structure and Formation (CLSF)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1462422
- Report Number(s):
- BNL-207910-2018-JAAM
Journal ID: ISSN 2055-0278
- Grant/Contract Number:
- SC0012704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Plants
- Additional Journal Information:
- Journal Volume: 4; Journal Issue: 5; Journal ID: ISSN 2055-0278
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Gou, Mingyue, Ran, Xiuzhi, Martin, Dwight W., and Liu, Chang -Jun. The scaffold proteins of lignin biosynthetic cytochrome P450 enzymes. United States: N. p., 2018.
Web. doi:10.1038/s41477-018-0142-9.
Gou, Mingyue, Ran, Xiuzhi, Martin, Dwight W., & Liu, Chang -Jun. The scaffold proteins of lignin biosynthetic cytochrome P450 enzymes. United States. doi:10.1038/s41477-018-0142-9.
Gou, Mingyue, Ran, Xiuzhi, Martin, Dwight W., and Liu, Chang -Jun. Mon .
"The scaffold proteins of lignin biosynthetic cytochrome P450 enzymes". United States. doi:10.1038/s41477-018-0142-9. https://www.osti.gov/servlets/purl/1462422.
@article{osti_1462422,
title = {The scaffold proteins of lignin biosynthetic cytochrome P450 enzymes},
author = {Gou, Mingyue and Ran, Xiuzhi and Martin, Dwight W. and Liu, Chang -Jun},
abstractNote = {Lignin is a complex and irregular biopolymer of cross-linked phenylpropanoid units in plant secondary cell walls. Its biosynthesis requires three endoplasmic reticulum (ER)-resident cytochrome P450 monooxygenases, C4H, C3'H and F5H, to establish the structural characteristics of its monomeric precursors. Those P450 enzymes were reported to associate with each other or potentially with other soluble monolignol biosynthetic enzymes to form enzyme complex or metabolone. However, molecular basis governing such enzyme or pathway organization remains elusive. Here we show that Arabidopsis membrane steroid binding proteins (MSBPs) serve as scaffold physically organizing monolignol P450 monooxygenases thereby regulating lignin biosynthetic process. We find that although C4H, C3'H and F5H are in spatial proximity to each other on ER membrane in vivo, they do not appear to directly interact with each other. Instead, two MSBP proteins physically interact with all three P450 enzymes and, moreover, MSBPs themselves associate as homo- and heteromers on the ER membrane, thereby organizing P450 clusters. Down-regulation of MSBPs does not affect the transcription levels of monolignol biosynthetic P450 genes but substantially impairs the stability and activity of the MSBP-interacting P450 enzymes and, consequently, the lignin deposition, the accumulation of soluble phenolics in monolignol branch but not in flavonoid pathway. Furthermore, our study suggests that MSBP proteins are the essential structural component in ER membrane that physically organize and stabilize the monolignol biosynthetic P450 enzyme complex; thereby, specifically controlling phenylpropanoid-monolignol branch biosynthesis.},
doi = {10.1038/s41477-018-0142-9},
journal = {Nature Plants},
number = 5,
volume = 4,
place = {United States},
year = {2018},
month = {4}
}
Web of Science
Works referenced in this record:
Lignin Biosynthesis
journal, June 2003
- Boerjan, Wout; Ralph, John; Baucher, Marie
- Annual Review of Plant Biology, Vol. 54, Issue 1, p. 519-546
Dap1p, a Heme-Binding Protein That Regulates the Cytochrome P450 Protein Erg11p/Cyp51p in Saccharomyces cerevisiae
journal, February 2005
- Mallory, J. C.; Crudden, G.; Johnson, B. L.
- Molecular and Cellular Biology, Vol. 25, Issue 5
Spectroscopic and Biochemical Characterization of Heme Binding to Yeast Dap1p and Mouse PGRMC1p †
journal, December 2005
- Ghosh, Kaushik; Thompson, Alisha M.; Goldbeck, Robert A.
- Biochemistry, Vol. 44, Issue 50
Cloning, Yeast Expression, and Characterization of the Coupling of Two Distantly Related Arabidopsis thaliana NADPH-Cytochrome P450 Reductases with P450 CYP73A5
journal, August 1997
- Urban, Philippe; Mignotte, Claudia; Kazmaier, Michaël
- Journal of Biological Chemistry, Vol. 272, Issue 31
New GATEWAY vectors for High Throughput Analyses of Protein–Protein Interactions by Bimolecular Fluorescence Complementation
journal, September 2009
- Gehl, Christian; Waadt, Rainer; Kudla, Jörg
- Molecular Plant, Vol. 2, Issue 5
Regiospecific hydroxylation of isoflavones by cytochrome P450 81E enzymes from Medicago truncatula
journal, November 2003
- Liu, Chang-Jun; Huhman, David; Sumner, Lloyd W.
- The Plant Journal, Vol. 36, Issue 4
Membrane protein complexes catalyze both 4- and 3-hydroxylation of cinnamic acid derivatives in monolignol biosynthesis
journal, December 2011
- Chen, H. -C.; Li, Q.; Shuford, C. M.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 52
Arabidopsis Membrane Steroid Binding Protein 1 Is Involved in Inhibition of Cell Elongation
journal, December 2004
- Yang, Xiao-Hua; Xu, Zhi-Hong; Xue, Hong-Wei
- The Plant Cell, Vol. 17, Issue 1
Purification of low-abundance Arabidopsis plasma-membrane protein complexes and identification of candidate components
journal, March 2009
- Qi, Yiping; Katagiri, Fumiaki
- The Plant Journal, Vol. 57, Issue 5
Evidence for enzyme complexes in the phenylpropanoid and flavonoid pathways
journal, September 1999
- Winkel-Shirley, Brenda
- Physiologia Plantarum, Vol. 107, Issue 1
Metabolon formation and metabolic channeling in the biosynthesis of plant natural products
journal, June 2005
- Jørgensen, Kirsten; Rasmussen, Anne Vinther; Morant, Marc
- Current Opinion in Plant Biology, Vol. 8, Issue 3
Membrane steroid-binding protein 1 (MSBP1) negatively regulates brassinosteroid signaling by enhancing the endocytosis of BAK1
journal, June 2009
- Song, Li; Shi, Qiu-Ming; Yang, Xiao-Hua
- Cell Research, Vol. 19, Issue 7
GATEWAY™ vectors for Agrobacterium-mediated plant transformation
journal, May 2002
- Karimi, Mansour; Inzé, Dirk; Depicker, Ann
- Trends in Plant Science, Vol. 7, Issue 5, p. 193-195
Dap1/PGRMC1 Binds and Regulates Cytochrome P450 Enzymes
journal, February 2007
- Hughes, Adam L.; Powell, David W.; Bard, Martin
- Cell Metabolism, Vol. 5, Issue 2
The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function
journal, February 2016
- Scott, E. E.; Wolf, C. R.; Otyepka, M.
- Drug Metabolism and Disposition, Vol. 44, Issue 4
NAC transcription factors NST1 and NST3 regulate pod shattering in a partially redundant manner by promoting secondary wall formation after the establishment of tissue identity
journal, December 2008
- Mitsuda, Nobutaka; Ohme-Takagi, Masaru
- The Plant Journal, Vol. 56, Issue 5
The MYB107 Transcription Factor Positively Regulates Suberin Biosynthesis
journal, December 2016
- Gou, Mingyue; Hou, Guichuan; Yang, Huijun
- Plant Physiology, Vol. 173, Issue 2
Colocalization of l-Phenylalanine Ammonia-Lyase and Cinnamate 4-Hydroxylase for Metabolic Channeling in Phenylpropanoid Biosynthesis
journal, October 2004
- Achnine, Lahoucine; Blancaflor, Elison B.; Rasmussen, Susanne
- The Plant Cell, Vol. 16, Issue 11
Bimolecular Fluorescence Complementation (BiFC) Analysis as a Probe of Protein Interactions in Living Cells
journal, June 2008
- Kerppola, Tom K.
- Annual Review of Biophysics, Vol. 37, Issue 1
K+ channel interactions detected by a genetic system optimized for systematic studies of membrane protein interactions
journal, August 2004
- Obrdlik, P.; El-Bakkoury, M.; Hamacher, T.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 33
Characterization of the adrenal-specific antigen IZA (inner zone antigen) and its role in the steroidogenesis
journal, February 2004
- Min, Li; Takemori, Hiroshi; Nonaka, Yasuki
- Molecular and Cellular Endocrinology, Vol. 215, Issue 1-2
Arabidopsis Kelch Repeat F-Box Proteins Regulate Phenylpropanoid Biosynthesis via Controlling the Turnover of Phenylalanine Ammonia-Lyase
journal, December 2013
- Zhang, Xuebin; Gou, Mingyue; Liu, Chang-Jun
- The Plant Cell, Vol. 25, Issue 12
Split ubiquitin as a sensor of protein interactions in vivo.
journal, October 1994
- Johnsson, N.; Varshavsky, A.
- Proceedings of the National Academy of Sciences, Vol. 91, Issue 22
Membrane Associated Progesterone Receptors: Promiscuous Proteins with Pleiotropic Functions – Focus on Interactions with Cytochromes P450
journal, March 2017
- Ryu, Chang S.; Klein, Kathrin; Zanger, Ulrich M.
- Frontiers in Pharmacology, Vol. 8
Emerging strategies of lignin engineering and degradation for cellulosic biofuel production
journal, April 2008
- Weng, Jing-Ke; Li, Xu; Bonawitz, Nicholas D.
- Current Opinion in Biotechnology, Vol. 19, Issue 2
Saccharomyces cerevisiae Dap1p, a Novel DNA Damage Response Protein Related to the Mammalian Membrane-Associated Progesterone Receptor
journal, April 2003
- Hand, Randal A.; Jia, Nan; Bard, Martin
- Eukaryotic Cell, Vol. 2, Issue 2
Molecular identification of adrenal inner zone antigen as a heme-binding protein: Molecular properties of adrenal inner zone antigen
journal, October 2005
- Min, Li; Strushkevich, Natallia V.; Harnastai, Ivan N.
- FEBS Journal, Vol. 272, Issue 22
Mutation of the Inducible ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE2 Alters Lignin Composition and Improves Saccharification
journal, October 2014
- Sundin, Lisa; Vanholme, Ruben; Geerinck, Jan
- Plant Physiology, Vol. 166, Issue 4
Linking genome and proteome by mass spectrometry: Large-scale identification of yeast proteins from two dimensional gels
journal, December 1996
- Shevchenko, A.; Jensen, O. N.; Podtelejnikov, A. V.
- Proceedings of the National Academy of Sciences, Vol. 93, Issue 25
The developing xylem transcriptome and genome-wide analysis of alternative splicing in Populus trichocarpa (black cottonwood) populations
journal, January 2013
- Bao, Hua; Li, Eryang; Mansfield, Shawn D.
- BMC Genomics, Vol. 14, Issue 1
Protein–Protein and Protein–Membrane Associations in the Lignin Pathway
journal, November 2012
- Bassard, Jean-Etienne; Richert, Ludovic; Geerinck, Jan
- The Plant Cell, Vol. 24, Issue 11
PGRMC1 (progesterone receptor membrane component 1): A targetable protein with multiple functions in steroid signaling, P450 activation and drug binding
journal, January 2009
- Rohe, Hannah J.; Ahmed, Ikhlas S.; Twist, Katherine E.
- Pharmacology & Therapeutics, Vol. 121, Issue 1
Transgene-Mediated and Elicitor-Induced Perturbation of Metabolic Channeling at the Entry Point into the Phenylpropanoid Pathway
journal, August 1999
- Rasmussen, Susanne; Dixon, Richard A.
- The Plant Cell, Vol. 11, Issue 8
Spectroscopic and Mutagenesis Studies of Human PGRMC1
journal, February 2015
- Kaluka, Daniel; Batabyal, Dipanwita; Chiang, Bing-Yu
- Biochemistry, Vol. 54, Issue 8
Membrane Steroid Binding Protein 1 (MSBP1) Stimulates Tropism by Regulating Vesicle Trafficking and Auxin Redistribution
journal, November 2008
- Yang, Xi; Song, Li; Xue, Hong-Wei
- Molecular Plant, Vol. 1, Issue 6
A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo
journal, April 1998
- Stagljar, I.; Korostensky, C.; Johnsson, N.
- Proceedings of the National Academy of Sciences, Vol. 95, Issue 9
Heteromeric Complex Formation between CYP2E1 and CYP1A2: Evidence for the Involvement of Electrostatic Interactions †
journal, December 2006
- Kelley, Rusty W.; Cheng, Dongmei; Backes, Wayne L.
- Biochemistry, Vol. 45, Issue 51
Development of series of gateway binary vectors, pGWBs, for realizing efficient construction of fusion genes for plant transformation
journal, July 2007
- Nakagawa, Tsuyoshi; Kurose, Takayuki; Hino, Takeshi
- Journal of Bioscience and Bioengineering, Vol. 104, Issue 1
Bimolecular Fluorescence Complementation Analysis of Cytochrome p450 2c2, 2e1, and Nadph-Cytochrome p450 Reductase Molecular Interactions in Living Cells
journal, June 2005
- Ozalp, Cengiz; Szczesna-Skorupa, Elzbieta; Kemper, Byron
- Drug Metabolism and Disposition, Vol. 33, Issue 9
Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance
journal, March 2016
- Kabe, Yasuaki; Nakane, Takanori; Koike, Ikko
- Nature Communications, Vol. 7, Issue 1
Tobacco Transcription Factor WRKY1 Is Phosphorylated by the MAP Kinase SIPK and Mediates HR-Like Cell Death in Tobacco
journal, October 2005
- Menke, Frank L. H.; Kang, Hong-Gu; Chen, Zhixiang
- Molecular Plant-Microbe Interactions, Vol. 18, Issue 10
Twin anchors of the soybean isoflavonoid metabolon: evidence for tethering of the complex to the endoplasmic reticulum by IFS and C4H
journal, March 2016
- Dastmalchi, Mehran; Bernards, Mark A.; Dhaubhadel, Sangeeta
- The Plant Journal, Vol. 85, Issue 6
Organization of multiple cytochrome P450s with NADPH-cytochrome P450 reductase in membranes
journal, May 2003
- Backes, Wayne L.; Kelley, Rusty W.
- Pharmacology & Therapeutics, Vol. 98, Issue 2
Cloning, Functional Expression, and Subcellular Localization of Multiple NADPH-Cytochrome P450 Reductases from Hybrid Poplar
journal, November 2002
- Ro, Dae-Kyun; Ehlting, Jürgen; Douglas, Carl J.
- Plant Physiology, Vol. 130, Issue 4
An Endoplasmic Reticulum-Derived Structure That Is Induced under Stress Conditions in Arabidopsis
journal, December 2002
- Matsushima, Ryo; Hayashi, Yasuko; Kondo, Maki
- Plant Physiology, Vol. 130, Issue 4
A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase
journal, September 2016
- Piel, Robert B.; Shiferaw, Mesafint T.; Vashisht, Ajay A.
- Biochemistry, Vol. 55, Issue 37
Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells
journal, August 2006
- Kerppola, Tom K.
- Nature Protocols, Vol. 1, Issue 3
An Engineered Monolignol 4- O -Methyltransferase Depresses Lignin Biosynthesis and Confers Novel Metabolic Capability in Arabidopsis
journal, July 2012
- Zhang, Kewei; Bhuiya, Mohammad-Wadud; Pazo, Jorge Rencoret
- The Plant Cell, Vol. 24, Issue 7
Split‐Ubiquitin System for Identifying Protein‐Protein Interactions in Membrane and Full‐Length Proteins
journal, October 2007
- Grefen, Christopher; Lalonde, Sylvie; Obrdlik, Petr
- Current Protocols in Neuroscience, Vol. 41, Issue 1
Works referencing / citing this record:
Transcriptomic analysis of early fruit development in Chinese white pear (Pyrus bretschneideri Rehd.) and functional identification of PbCCR1 in lignin biosynthesis
journal, October 2019
- Su, Xueqiang; Zhao, Yu; Wang, Han
- BMC Plant Biology, Vol. 19, Issue 1
4-Coumarate 3-hydroxylase in the lignin biosynthesis pathway is a cytosolic ascorbate peroxidase
journal, April 2019
- Barros, Jaime; Escamilla-Trevino, Luis; Song, Luhua
- Nature Communications, Vol. 10, Issue 1
Identification of genetic loci associated with forage quality in response to water deficit in autotetraploid alfalfa (Medicago sativa L.)
journal, July 2020
- Lin, Sen; Medina, Cesar Augusto; Boge, Bill
- BMC Plant Biology, Vol. 20, Issue 1
Comparative functional genomics analysis of cytochrome P450 gene superfamily in wheat and maize
journal, March 2020
- Li, Yixuan; Wei, Kaifa
- BMC Plant Biology, Vol. 20, Issue 1
Secondary cell wall biosynthesis
journal, November 2018
- Zhong, Ruiqin; Cui, Dongtao; Ye, Zheng‐Hua
- New Phytologist, Vol. 221, Issue 4
Lignocellulosic Biomass as Source for Lignin-Based Environmentally Benign Antioxidants
journal, October 2018
- Alzagameem, Abla; Khaldi-Hansen, Basma; Büchner, Dominik
- Molecules, Vol. 23, Issue 10
Glucosinolate and phenylpropanoid biosynthesis are linked by proteasome‐dependent degradation of PAL
journal, September 2019
- Kim, Jeong Im; Zhang, Xuebin; Pascuzzi, Pete E.
- New Phytologist, Vol. 225, Issue 1
Metabolons in plant primary and secondary metabolism
journal, July 2019
- Obata, Toshihiro
- Phytochemistry Reviews, Vol. 18, Issue 6
4-Coumarate 3-hydroxylase in the lignin biosynthesis pathway is a cytosolic ascorbate peroxidase
journal, April 2019
- Barros, Jaime; Escamilla-Trevino, Luis; Song, Luhua
- Nature Communications, Vol. 10, Issue 1
Proanthocyanidin subunit composition determined by functionally diverged dioxygenases
journal, November 2018
- Jun, Ji Hyung; Xiao, Xirong; Rao, Xiaolan
- Nature Plants, Vol. 4, Issue 12
Glycoside‐specific glycosyltransferases catalyze regio‐selective sequential glucosylations for a sesame lignan, sesaminol triglucoside
journal, December 2019
- Ono, Eiichiro; Waki, Toshiyuki; Oikawa, Daiki
- The Plant Journal, Vol. 101, Issue 5
Enzyme-Enzyme Interactions in Monolignol Biosynthesis
journal, January 2019
- Wang, Jack P.; Liu, Baoguang; Sun, Yi
- Frontiers in Plant Science, Vol. 9
Dynamic metabolic solutions to the sessile life style of plants
journal, January 2018
- Knudsen, Camilla; Gallage, Nethaji Janeshawari; Hansen, Cecilie Cetti
- Natural Product Reports, Vol. 35, Issue 11
Passive membrane transport of lignin-related compounds
journal, October 2019
- Vermaas, Josh V.; Dixon, Richard A.; Chen, Fang
- Proceedings of the National Academy of Sciences, Vol. 116, Issue 46
Lignin-Only Polymeric Materials Based on Unmethylated Unfractionated Kraft and Ball-Milled Lignins Surpass Polyethylene and Polystyrene in Tensile Strength
journal, December 2019
- Chen, Yi-ru; Sarkanen, Simo; Wang, Yun-Yan
- Molecules, Vol. 24, Issue 24
Formation of Flavonoid Metabolons: Functional Significance of Protein-Protein Interactions and Impact on Flavonoid Chemodiversity
journal, July 2019
- Nakayama, Toru; Takahashi, Seiji; Waki, Toshiyuki
- Frontiers in Plant Science, Vol. 10
Lignin biosynthesis: old roads revisited and new roads explored
journal, December 2019
- Dixon, Richard A.; Barros, Jaime
- Open Biology, Vol. 9, Issue 12
Enhanced Enzyme Activity through Scaffolding on Customizable Self‐Assembling Protein Filaments
journal, March 2019
- Lim, Samuel; Jung, Gi Ahn; Glover, Dominic J.
- Small, Vol. 15, Issue 20
The lignin toolbox of the model grass Setaria viridis
journal, June 2019
- Ferreira, Sávio Siqueira; Simões, Marcella Siqueira; Carvalho, Gabriel Garon
- Plant Molecular Biology, Vol. 101, Issue 3
Lignin-Derived Biomaterials for Drug Release and Tissue Engineering
journal, July 2018
- Witzler, Markus; Alzagameem, Abla; Bergs, Michel
- Molecules, Vol. 23, Issue 8
Transcriptomic analysis of early fruit development in Chinese white pear (Pyrus bretschneideri Rehd.) and functional identification of PbCCR1 in lignin biosynthesis
journal, October 2019
- Su, Xueqiang; Zhao, Yu; Wang, Han
- BMC Plant Biology, Vol. 19, Issue 1
Formation of Flavonoid Metabolons: Functional Significance of Protein-Protein Interactions and Impact on Flavonoid Chemodiversity
journal, July 2019
- Nakayama, Toru; Takahashi, Seiji; Waki, Toshiyuki
- Frontiers in Plant Science, Vol. 10
Lignin-Derived Biomaterials for Drug Release and Tissue Engineering
journal, July 2018
- Witzler, Markus; Alzagameem, Abla; Bergs, Michel
- Molecules, Vol. 23, Issue 8
The lignin toolbox of the model grass Setaria viridis
journal, June 2019
- Ferreira, Sávio Siqueira; Simões, Marcella Siqueira; Carvalho, Gabriel Garon
- Plant Molecular Biology, Vol. 101, Issue 3