Abstract
KNOTTED-LIKE HOMEOBOX (KNOX) proteins are homeodomain containing transcription factors, and regulate many aspects of plant development through homo or heterodimerization with another group of TALE transcription factors known as BELL. In Medicago truncatula the MtKNOX3 gene is involved in nodule development. In this work, we hypothesized that MtKNOX3 involvement in the activation of cytokinin signaling during nodule development could be through heterodimerization with BELL proteins. Thereby, the expression of different BELL genes in Medicago was analyzed, and it was shown that the expression of Medtr8g078480 and Medtr8g098815 genes increases during nodule development. Besides, the Medtr8g078480 shows a co-expression pattern with MtKNOX3 at different developmental stages of nodule development. Afterward, the interaction of MtKNOX3 with the MtBELL1-2 (Medtr8g078480) protein was shown using docking, and their stability was analyzed by molecular dynamic simulation and mmpbsa methods. Moreover, the stability of MtKNOX3- Medtr8g078480 heterodimers was compared with the MtKNOX3 homodimer.
Similar content being viewed by others
REFERENCES
Hay A., Tsiantis M. 2010. KNOX genes: Versatile regulators of plant development and diversity. Development. 137 (19), 3153‒3165.
Bharathan G., Janssen B.-J., Kellogg E.A., Sinha N. 1999. Phylogenetic relationships and evolution of the KNOTTED class of plant homeodomain proteins. Mol. Biol. Evol. 16 (4), 553‒563.
Kerstetter R., Vollbrecht E., Lowe B., Veit B., Yamaguchi J., Hake S. 1994. Sequence analysis and expression patterns divide the maize knotted1-like homeobox genes into two classes. Plant Cell. 6 (12), 1877‒1887.
Mukherjee K., Brocchieri L., Bürglin T.R. 2009. A comprehensive classification and evolutionary analysis of plant homeobox genes. Mol. Biol. Evol. 26 (12), 2775‒2794.
Belles-Boix E., Hamant O., Witiak S.M., Morin H., Traas J., Pautot V. 2006. KNAT6: An Arabidopsis homeobox gene involved in meristem activity and organ separation. Plant Cell. 18 (8), 1900‒1907.
Byrne M.E., Simorowski J., Martiensse R.A. 2002. ASYMMETRIC LEAVES1 reveals knox gene redundancy in Arabidopsis. Development. 129 (8), 1957‒1965.
Long J.A., Moan E.I., Medford J.I., Barton M.K. 1996. A member of the KNOTTED class of homeodomain proteins encoded by the STM gene of Arabidopsis. Nature. 379 (6560), 66‒69.
Bharathan G., Goliber T.E., Moore C., Kessler S., Pham T., Sinha N.R. 2002. Homologies in leaf form inferred from KNOXI gene expression during development. Science. 296 (5574), 1858‒1860.
Hareven D., Gutfinger T., Parnis A., Eshed Y., Lifschitz E. 1996. The making of a compound leaf: Genetic manipulation of leaf architecture in tomato. Cell. 84 (5), 735‒744.
Wang Y., Jiao Y. 2018. Axillary meristem initiation—A way to branch out. Curr. Opin. Plant Biol. 41, 61‒66.
Yang Q., Cong T., Yao Y., Cheng T., Yuan C., Zhang Q. 2023. KNOX genes were involved in regulating axillary bud formation of Chrysanthemum × morifolium. Int. J. Mol. Sci. 24 (8), 7081.
Li E., Bhargava A., Qiang W., Friedmann M.C., Forneris N., Savidge R.A., Johnson L.A., Mansfield S.D., Ellis B.E., Douglas C.J. 2012. The Class II KNOX gene KNAT7 negatively regulates secondary wall formation in Arabidopsis and is functionally conserved in Populus. New Phytol. 194 (1), 102‒115.
Serikawa K.A., Martinez-Laborda A., Kim H.S., Zambryski P.C. 1997. Localization of expression of KNAT3, a class 2 knotted1-like gene. Plant J. 11 (4), 853‒861.
Truernit E., Siemering K.R., Hodge S., Grbic V., Haseloff J. 2006. A map of KNAT gene expression in the Arabidopsis root. Plant Mol. Biol. 60 (1), 1‒20.
Azarakhsh M., Kirienko A., Zhukov V., Lebedeva M., Dolgikh E., Lutova L. 2015. KNOTTED1-LIKE HOMEOBOX 3: A new regulator of symbiotic nodule development. J. Exp. Bot. 66 (22), 7181‒7195.
Di Giacomo E., Laffont C., Sciarra F., Iannelli M.A., Frugier F., Frugis G. 2017. KNAT3/4/5-like class 2 KNOX transcription factors are involved in Medicago truncatula symbiotic nodule organ development. New Phytol. 213 (2), 822‒837.
Truernit E., Haseloff J. 2007. A role for KNAT class II genes in root development. Plant Signal. Behav. 2 (1), 10‒12.
Magnani E., Hake S. 2008. KNOX lost the OX: The Arabidopsis KNATM gene defines a novel class of KNOX transcriptional regulators missing the homeodomain. Plant Cell. 20 (4), 875‒887.
Nagasaki H., Sakamoto T., Sato Y., Matsuoka M. 2001. Functional analysis of the conserved domains of a rice KNOX homeodomain protein, OSH15. Plant Cell. 13 (9), 2085‒2098.
Bellaoui M., Pidkowich M.S., Samach A., Kushalap-pa K., Kohalmi S.E., Modrusan Z., Crosby W.L., Haughn G.W. 2001. The Arabidopsis BELL1 and KNOX TALE homeodomain proteins interact through a domain conserved between plants and animals. Plant Cell. 13 (11), 2455‒2470.
Bhatt A.M., Etchells J.P., Canales C., Lagodienko A., Dickinson H. 2004. VAAMANA‒a BEL1-like homeodomain protein, interacts with KNOX proteins BP and STM and regulates inflorescence stem growth in Arabidopsis. Gene. 328, 103‒111.
Cole M., Nolte C., Werr W. 2006. Nuclear import of the transcription factor SHOOT MERISTEMLESS depends on heterodimerization with BLH proteins expressed in discrete sub-domains of the shoot apical meristem of Arabidopsis thaliana. Nucleic Acids Res. 34 (4), 1281‒1292.
Niu X., Fu D. 2022. The roles of BLH transcription factors in plant development and environmental response. Int. J. Mol. Sci. 23 (7), 3731.
Kim D., Cho Y.H., Ryu H., Kim Y., Kim T.H., Hwang I. 2013. BLH1 and KNAT3 modulate ABA responses during germination and early seedling development in Arabidopsis. Plant J. 75 (5), 755‒766.
Rutjens B., Bao D., Van Eck-Stouten E., Brand M., Smeekens S., Proveniers M. 2009. Shoot apical meristem function in Arabidopsis requires the combined activities of three BEL1-like homeodomain proteins. Plant J. 58 (4), 641‒654.
Smith H.M., Boschke I., Hake S. 2002. Selective interaction of plant homeodomain proteins mediates high DNA-binding affinity. Proc. Natl. Acad. Sci . U. S. A. 99 (14), 9579‒9584.
Chen H., Banerjee A.K., Hannapel D.J. 2004. The tandem complex of BEL and KNOX partners is required for transcriptional repression of ga20ox1. Plant J. 38 (2), 276‒284.
Jasinski S., Piazza P., Craft J., Hay A., Woolley L., Rieu I., Phillips A., Hedden P., Tsiantis M. 2005. Curr. Biol. 15 (17), 1560‒1565.
Sakamoto T., Kamiya N., Ueguchi-Tanaka M., Iwahori S., Matsuoka M. 2001. KNOX homeodomain protein directly suppresses the expression of a gibberellin biosynthetic gene in the tobacco shoot apical meristem. Genes Dev. 15 (5), 581‒590.
Heckmann A.B., Sandal N., Bek A.S., Madsen L.H., Jurkiewicz A., Nielsen M.W., Tirichine L., Stougaard J. 2011. Cytokinin induction of root nodule primordia in Lotus japonicus is regulated by a mechanism operating in the root cortex. Mol. Plant–Microbe Interact. 24 (11), 1385‒1395.
Murray J.D., Karas B.J., Sato S., Tabata S., Amyot L., Szczyglowski K. 2007. Science. 315 (5808), 101‒104.
Tirichine L., Sandal N., Madsen L.H., Radutoiu S., Albrektsen A.S., Sato S., Asamizu E., Tabata S., Stougaard J. 2007. A gain-of-function mutation in a cytokinin receptor triggers spontaneous root nodule organogenesis. Science. 315 (5808), 104‒107.
Azarakhsh M., Rumyantsev A.M., Lebedeva M.A., Lutova L.A. 2020. Cytokinin biosynthesis genes expressed during nodule organogenesis are directly regulated by the KNOX3 protein in Medicago truncatula. PloS One. 15 (4), e0232352.
Fåhraeus G. 1957. The infection of clover root hairs by nodule bacteria studied by a simple glass slide technique. J. Gen. Microbiol. 16 (2), 374‒381.
Livak K.J. Schmittgen T.D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and 2−ΔΔCT method. Methods. 25 (4), 402‒408.
Yang J., Yan R., Roy A., Xu D., Poisson J., Zhang Y. 2015. The I-TASSER Suite: Protein structure and function prediction. Nat. Methods. 12 (1), 7‒8.
Kozakov D., Hall D.R., Xia B., Porter K.A., Padhorny D., Yueh C., Beglov D., Vajda S. 2017. The ClusPro web server for protein−protein docking. Nat. Protoc. 2 (2), 255‒278.
Smith H.M., Campbell B.C., Hake S. 2004. Competence to respond to floral inductive signals requires the homeobox genes PENNYWISE and POUND-FOOLISH. Curr. Biol. 14 (9), 812‒817.
Dolgikh A.V., Rudaya E.S., Dolgikh E.A. 2020. Identification of BELL transcription factors involved in nodule initiation and development in the legumes Pisum sativum and Medicago truncatula. Plants. 9 (12), 1808.
Bürglin T.R. 1997. Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals. Nucleic Acids Res. 25 (21), 4173‒4180.
Bürglin T.R. 1998. The PBC domain contains a MEI-NOX domain: coevolution of Hox and TALE homeobox genes? Dev. Genes Evol. 208 (2), 113‒116.
Berthelsen J., Zappavigna V., Ferretti E., Mavilio F., Blasi F. 1998. The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity. EMBO J. 17 (5), 1434‒1445.
Hackbusch J., Richter K., Müller J., Salamini F., Uhrig J.F. 2005. A central role of Arabidopsis thaliana ovate family proteins in networking and subcellular localization of 3-aa loop extension homeodomain proteins. Proc. Natl. Acad. Sci. U. S. A. 102 (13), 4908‒4912.
Qin W., Yin Q., Chen J., Zhao X., Yue F., He J., Yang L., Liu L., Zeng Q., Lu F., Mitsuda N., Ohme-Takagi M., Wu A.M. 2020. The class II KNOX transcription factors KNAT3 and KNAT7 synergistically regulate monolignol biosynthesis in arabidopsis. J. Exp. Bot. 71 (18), 5469‒5483.
Zhou J., Qi Y., Nie J., Guo L., Luo M., McLellan H., Boevink P.C., Birch P.R., Tian Z. 2022. A phytophthora effector promotes homodimerization of host transcription factor StKNOX3 to enhance susceptibility. J. Exp. Bot. 73 (19), 6902‒6915.
Valdés-Tresanco M.S., Valdés-Tresanco M.E., Valiente P.A., Moreno E. 2021. gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS. J. Chem. Theory Comput. 17 (10), 6281‒6291.
Funding
This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.
Author information
Authors and Affiliations
Contributions
Material preparation, data collection, and analysis were performed by Mahboobeh Azarakhsh, original draft preparation: Mahboobeh Azarakhsh, review and editing, Mahboobeh Azarakhsh, Maria Lebedeva, and Vijay Vishvakarma. All authors have read and agreed to the published version of the manuscript.
Corresponding author
Ethics declarations
CONFLICT OF INTEREST
The authors of this work declare that they have no conflicts of interest.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
This work does not contain any studies involving human and animal subjects.
Additional information
Publisher’s Note.
Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
About this article
Cite this article
Azarakhsh, M., Lebedeva, M. & Vishvakarma, V.K. Modeling Protein–Protein Interaction of the KNOTTED-LIKE HOMEOBOX 3 Protein Involved in Symbiotic Nodule Development in Medicago truncatula. Mol Biol 58, 336–345 (2024). https://doi.org/10.1134/S0026893324020031
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893324020031