title: Structural basis for LEAFY floral switch function and similarity with helix-turn-helix proteins.
abstract: The LEAFY (LFY) protein is a key regulator of flower development in angiosperms. Its gradually increased expression governs the sharp floral transition, and LFY subsequently controls the patterning of flower meristems by inducing the expression of floral homeotic genes. Despite a wealth of genetic data, how LFY functions at the molecular level is poorly understood. Here, we report crystal structures for the DNA-binding domain of Arabidopsis thaliana LFY bound to two target promoter elements. LFY adopts a novel seven-helix fold that binds DNA as a cooperative dimer, forming base-specific contacts in both the major and minor grooves. Cooperativity is mediated by two basic residues and plausibly accounts for LFY's effectiveness in triggering sharp developmental transitions. Our structure reveals an unexpected similarity between LFY and helix-turn-helix proteins, including homeodomain proteins known to regulate morphogenesis in higher eukaryotes. The appearance of flowering plants has been linked to the molecular evolution of LFY. Our study provides a unique framework to elucidate the molecular mechanisms underlying floral development and the evolutionary history of flowering plants.
authors.affiliation: Laboratoire Physiologie Cellulaire Végétale, UMR5168, Centre National de la Recherche Scientifique, Commissariat à l'énergie atomique, Institut National de la Recherche Agronomique, Université Joseph Fourier, Grenoble, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Hamès
authors.forename: Denis
authors.initials: D
authors.lastname: Ptchelkine
authors.forename: Clemens
authors.initials: C
authors.lastname: Grimm
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Thevenon
authors.forename: Edwige
authors.initials: E
authors.lastname: Moyroud
authors.forename: Francine
authors.initials: F
authors.lastname: Gérard
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Martiel
authors.forename: Reyes
authors.initials: R
authors.lastname: Benlloch
authors.forename: François
authors.initials: F
authors.lastname: Parcy
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Müller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000033:anatomy & histology / Q000502:physiology*; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D035264:Flowers / Q000502:physiology*; D019077:Helix-Turn-Helix Motifs; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; C074747:LFY protein, Arabidopsis; D046911:Macromolecular Substances; D014157:Transcription Factors; D004247:DNA
references.citation: Plant Cell. 1999 Jun;11(6):1007-18
references.pmid: 10368173
references.citation: Development. 2002 May;129(9):2079-86
references.pmid: 11959818
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Annu Rev Biochem. 1994;63:487-526
references.pmid: 7979246
references.citation: Cell. 1990 Dec 21;63(6):1311-22
references.pmid: 1702033
references.citation: Nature. 1998 Oct 8;395(6702):561-6
references.pmid: 9783581
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1445-50
references.pmid: 11567158
references.citation: Nucleic Acids Res. 1998 Apr 1;26(7):1848-50
references.pmid: 9512562
references.citation: Nat Rev Genet. 2003 Jul;4(7):559-66
references.pmid: 12838347
references.citation: Curr Biol. 1997 Feb 1;7(2):95-104
references.pmid: 9016705
references.citation: J Mol Evol. 1999 Sep;49(3):301-9
references.pmid: 10473770
references.citation: Mol Cell. 2001 Nov;8(5):937-46
references.pmid: 11741530
references.citation: Biochem Cell Biol. 2000;78(5):629-38
references.pmid: 11103953
references.citation: Cell. 1992 May 29;69(5):843-59
references.pmid: 1350515
references.citation: Ann Bot. 2007 Sep;100(3):603-19
references.pmid: 17670752
references.citation: Development. 2003 Aug;130(16):3735-45
references.pmid: 12835390
references.citation: Cell. 2001 Jun 15;105(6):793-803
references.pmid: 11440721
references.citation: EMBO J. 2004 Nov 10;23(22):4384-93
references.pmid: 15510218
references.citation: Nat Rev Genet. 2001 Mar;2(3):186-95
references.pmid: 11256070
references.citation: Cell. 2007 Nov 2;131(3):530-43
references.pmid: 17981120
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Cell. 1990 Nov 2;63(3):455-6
references.pmid: 2225060
references.citation: Science. 2005 Apr 8;308(5719):260-3
references.pmid: 15821093
references.citation: Dev Cell. 2002 Feb;2(2):135-42
references.pmid: 11832239
references.citation: Curr Opin Plant Biol. 2000 Oct;3(5):423-34
references.pmid: 11019812
references.citation: Nat Rev Genet. 2007 Sep;8(9):675-88
references.pmid: 17703238
references.citation: Plant J. 1999 Dec;20(6):685-93
references.pmid: 10652140
references.citation: EMBO J. 1997 Oct 1;16(19):6044-54
references.pmid: 9312061
references.citation: Biochemistry. 2007 Sep 11;46(36):10328-38
references.pmid: 17705401
references.citation: Cell. 2001 Jun 15;105(6):805-14
references.pmid: 11440722
references.citation: Annu Rev Immunol. 1998;16:569-92
references.pmid: 9597142
references.citation: Trends Plant Sci. 2002 Jul;7(7):297-301
references.pmid: 12119166
references.citation: FEBS Lett. 1997 Apr 1;405(3):373-7
references.pmid: 9108321
references.citation: Nature. 2007 Dec 20;450(7173):1184-9
references.pmid: 18097399
references.citation: Plant Physiol. 2005 Sep;139(1):18-26
references.pmid: 16166257
references.citation: Nat Struct Biol. 1997 Apr;4(4):269-75
references.pmid: 9095194
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Plant Cell. 2003 Jun;15(6):1296-309
references.pmid: 12782724
references.citation: EMBO J. 2002 Mar 1;21(5):1210-8
references.pmid: 11867549
references.citation: Methods Enzymol. 1997;276:472-494
references.pmid: 27799110
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references.pmid: 12393927
references.citation: Development. 2003 Jun;130(11):2385-95
references.pmid: 12702653
references.citation: J Theor Biol. 2000 Mar 21;203(2):117-33
references.pmid: 10704297
references.citation: Genes Dev. 1999 May 15;13(10):1263-75
references.pmid: 10346815
references.citation: Development. 1998 Feb;125(4):733-42
references.pmid: 9435293
references.citation: Proteins. 1992 Oct;14(2):309-23
references.pmid: 1409577
references.citation: Plant Mol Biol. 2006 Apr;60(6):855-70
references.pmid: 16724257
references.citation: Nature. 1991 Sep 5;353(6339):31-7
references.pmid: 1715520
references.citation: Dev Genes Evol. 2000 Dec;210(12):644-50
references.pmid: 11151303
references.citation: EMBO J. 1998 Oct 15;17(20):5998-6009
references.pmid: 9774343
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
references.pmid: 10089316
references.citation: Methods. 1998 Sep;16(1):3-20
references.pmid: 9774512
references.citation: Nat Struct Mol Biol. 2004 Jul;11(7):656-63
references.pmid: 15170177
references.citation: Microb Cell Fact. 2005 Dec 13;4:34
references.pmid: 16351710
references.citation: FEMS Microbiol Rev. 2005 Apr;29(2):231-62
references.pmid: 15808743
references.citation: Genetics. 1997 Jan;145(1):5-9
references.pmid: 9017384
references.citation: Science. 1999 Jul 23;285(5427):585-7
references.pmid: 10417388
references.citation: J Mol Biol. 1993 Sep 5;233(1):123-38
references.pmid: 8377180
references.citation: Development. 2008 Apr;135(7):1235-45
references.pmid: 18287201