leucine zippers


Summary: DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.

Top Publications

  1. Croasdale R, Ivins F, Muskett F, Daviter T, Scott D, Hardy T, et al. An undecided coiled coil: the leucine zipper of Nek2 kinase exhibits atypical conformational exchange dynamics. J Biol Chem. 2011;286:27537-47 pubmed publisher
    b>Leucine zippers are oligomerization domains used in a wide range of proteins. Their structure is based on a highly conserved heptad repeat sequence in which two key positions are occupied by leucines...
  2. Shin D, Koo Y, Lee J, Lee H, Baek D, Lee S, et al. Athb-12, a homeobox-leucine zipper domain protein from Arabidopsis thaliana, increases salt tolerance in yeast by regulating sodium exclusion. Biochem Biophys Res Commun. 2004;323:534-40 pubmed
    ..These results suggest that Athb-12 is a putative transcription factor that may be involved in NaCl stress responses in plants. ..
  3. Robischon M, Du J, Miura E, Groover A. The Populus class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems. Plant Physiol. 2011;155:1214-25 pubmed publisher
    ..Together, these results suggest that PRE plays a fundamental role in the initiation of the cambium and in regulating the patterning of secondary vascular tissues. ..
  4. Steinmetz M, Jelesarov I, Matousek W, Honnappa S, Jahnke W, Missimer J, et al. Molecular basis of coiled-coil formation. Proc Natl Acad Sci U S A. 2007;104:7062-7 pubmed
    ..Our findings provide a general explanation for the molecular mechanism of coiled-coil formation. ..
  5. Cannarile L, Cuzzocrea S, Santucci L, Agostini M, Mazzon E, Esposito E, et al. Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis. Gastroenterology. 2009;136:530-41 pubmed publisher
    ..Together these results demonstrate that GILZ mimics the effects of glucocorticoids, suggesting a contribution of this protein to the anti-inflammatory activity of glucocorticoids in Th1-induced colitis. ..
  6. Harris J, Hrmova M, Lopato S, Langridge P. Modulation of plant growth by HD-Zip class I and II transcription factors in response to environmental stimuli. New Phytol. 2011;190:823-37 pubmed publisher
    ..The in planta implications of these protein-protein associations and the similarities in cis element binding are not clear. ..
  7. Sorin C, Salla Martret M, Bou Torrent J, Roig Villanova I, Martinez Garcia J. ATHB4, a regulator of shade avoidance, modulates hormone response in Arabidopsis seedlings. Plant J. 2009;59:266-77 pubmed publisher
    ..In particular, we propose ATHB4 as a new shade signaling component that participates in integrating shade perception and hormone-mediated growth. ..
  8. Deng X, Phillips J, Bräutigam A, Engström P, Johannesson H, Ouwerkerk P, et al. A homeodomain leucine zipper gene from Craterostigma plantagineum regulates abscisic acid responsive gene expression and physiological responses. Plant Mol Biol. 2006;61:469-89 pubmed
    ..CpHB-7 gene expression is also linked to early organ development, leading to the suggestion that CpHB-7 is functionally similar to the Arabidopsis transcription factor, ATHB-6...
  9. Prigge M, Clark S. Evolution of the class III HD-Zip gene family in land plants. Evol Dev. 2006;8:350-61 pubmed
    ..Comparison of the expression domains of flowering and nonflowering plant homologs indicate an ancestral role in vascular development and organ initiation but not in specifying organ polarity, a prominent role for angiosperm homologs. ..

More Information


  1. Elhiti M, Stasolla C. Structure and function of homodomain-leucine zipper (HD-Zip) proteins. Plant Signal Behav. 2009;4:86-8 pubmed
    ..HD-Zip IV proteins play significant roles during anthocyanin accumulation, differentiation of epidermal cells, trichome formation and root development. ..
  2. Crooks R, Rao T, Mason J. Truncation, randomization, and selection: generation of a reduced length c-Jun antagonist that retains high interaction stability. J Biol Chem. 2011;286:29470-9 pubmed publisher
    ..However, antagonists of reduced length are worthy of perusal from the point of view of synthetic cost as well as identifying the smallest functional unit that is required for binding. ..
  3. Satou Y, Yasunaga J, Yoshida M, Matsuoka M. HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. Proc Natl Acad Sci U S A. 2006;103:720-5 pubmed
    ..Thus, the single HBZ gene has bimodal functions in two different molecular forms. The growth-promoting activity of HBZ RNA likely plays an important role in oncogenesis by HTLV-I. ..
  4. Rueda E, Dezar C, Gonzalez D, Chan R. Hahb-10, a sunflower homeobox-leucine zipper gene, is regulated by light quality and quantity, and promotes early flowering when expressed in Arabidopsis. Plant Cell Physiol. 2005;46:1954-63 pubmed
    ..We propose that Hahb-10 functions in a signalling cascade(s) that control(s) plant responses to light quality and quantity, and may also be involved in gibberellin transduction pathways. ..
  5. Qin Y, Li D, Wu Y, Liu Z, Zhang J, Zheng Y, et al. Three cotton homeobox genes are preferentially expressed during early seedling development and in response to phytohormone signaling. Plant Cell Rep. 2010;29:1147-56 pubmed publisher
    ..The results suggested that the three HB genes may function in early seedling development of cotton and in response to gibberellin signaling...
  6. Son O, Hur Y, Kim Y, Lee H, Kim S, Kim M, et al. ATHB12, an ABA-inducible homeodomain-leucine zipper (HD-Zip) protein of Arabidopsis, negatively regulates the growth of the inflorescence stem by decreasing the expression of a gibberellin 20-oxidase gene. Plant Cell Physiol. 2010;51:1537-47 pubmed publisher
    ..ABA-treated protoplasts also showed increased ATHB12 expression and reduced GA20ox1 expression. These findings all suggest that ATHB12 negatively regulates the expression of a GA 20-oxidase gene in inflorescence stems. ..
  7. Javelle M, Vernoud V, Dep ge Fargeix N, Arnould C, Oursel D, Domergue F, et al. Overexpression of the epidermis-specific homeodomain-leucine zipper IV transcription factor Outer Cell Layer1 in maize identifies target genes involved in lipid metabolism and cuticle biosynthesis. Plant Physiol. 2010;154:273-86 pubmed publisher
    ..Our data demonstrate that, in addition to AP2/EREBP and MYB-type transcription factors, members of the HD-ZIP IV family contribute to the transcriptional regulation of genes involved in cuticle biosynthesis...
  8. Prigge M, Otsuga D, Alonso J, Ecker J, Drews G, Clark S. Class III homeodomain-leucine zipper gene family members have overlapping, antagonistic, and distinct roles in Arabidopsis development. Plant Cell. 2005;17:61-76 pubmed
    ..Differences in expression patterns explain some of these genetic interactions, whereas other interactions are likely attributable to differences in protein function as indicated by cross-complementation studies. ..
  9. Magliery T, Wilson C, Pan W, Mishler D, Ghosh I, Hamilton A, et al. Detecting protein-protein interactions with a green fluorescent protein fragment reassembly trap: scope and mechanism. J Am Chem Soc. 2005;127:146-57 pubmed
    ..Using a library of antiparallel leucine zippers, we have shown that the screen can detect very weak interactions (K(D) approximately 1 mM)...
  10. Bensmihen S, Giraudat J, Parcy F. Characterization of three homologous basic leucine zipper transcription factors (bZIP) of the ABI5 family during Arabidopsis thaliana embryo maturation. J Exp Bot. 2005;56:597-603 pubmed
    ..Endogenous EEL, AREB3, and AtbZIP67 transcripts could be specifically reduced, but no visible defects could be observed during seed maturation. ..
  11. Hu R, Chi X, Chai G, Kong Y, He G, Wang X, et al. Genome-wide identification, evolutionary expansion, and expression profile of homeodomain-leucine zipper gene family in poplar (Populus trichocarpa). PLoS ONE. 2012;7:e31149 pubmed publisher
    ..Taken together, these observations may lay the foundation for future functional analysis of Populus HD-ZIP genes to unravel their biological roles. ..
  12. Smith Z, Long J. Control of Arabidopsis apical-basal embryo polarity by antagonistic transcription factors. Nature. 2010;464:423-6 pubmed publisher
    ..Furthermore, genetic and misexpression studies show an antagonistic relationship between the PLT and HD-ZIP III genes in specifying the root and shoot poles. ..
  13. Dezar C, Gago G, Gonzalez D, Chan R. Hahb-4, a sunflower homeobox-leucine zipper gene, is a developmental regulator and confers drought tolerance to Arabidopsis thaliana plants. Transgenic Res. 2005;14:429-40 pubmed
    ..Since Hahb-4 is a transcription factor, we propose that it may participate in the regulation of the expression of genes involved in developmental responses of plants to desiccation. ..
  14. Vernoud V, Laigle G, Rozier F, Meeley R, Perez P, Rogowsky P. The HD-ZIP IV transcription factor OCL4 is necessary for trichome patterning and anther development in maize. Plant J. 2009;59:883-94 pubmed publisher
    ..Taken together these results suggest that OCL4 inhibits trichome development and influences division and/or differentiation of the anther cell wall. ..
  15. Côté C, Boileau F, Roy V, Ouellet M, Levasseur C, Morency M, et al. Gene family structure, expression and functional analysis of HD-Zip III genes in angiosperm and gymnosperm forest trees. BMC Plant Biol. 2010;10:273 pubmed publisher
    ..We characterised and compared HD-Zip III gene family in an angiosperm tree, Populus spp. (poplar), and the gymnosperm Picea glauca (white spruce), representing two highly evolutionarily divergent groups...
  16. Kim Y, Son O, Kim M, Nam K, Kim G, Lee M, et al. ATHB23, an Arabidopsis class I homeodomain-leucine zipper gene, is expressed in the adaxial region of young leaves. Plant Cell Rep. 2007;26:1179-85 pubmed
    ..These results indicate that ATHB23 is under the control of GA and other activators such as PHB, and is involved in establishing polarity during leaf development. ..
  17. Su Z, Lee S, Emdad L, Lebdeva I, Gupta P, Valerie K, et al. Cloning and characterization of SARI (suppressor of AP-1, regulated by IFN). Proc Natl Acad Sci U S A. 2008;105:20906-11 pubmed publisher
    ..These findings uncover a novel mode of IFN-induced anti-tumor growth suppression and suggest potential gene therapy applications for SARI. ..
  18. Ohshima T, Mukai R, Nakahara N, Matsumoto J, Isono O, Kobayashi Y, et al. HTLV-1 basic leucine-zipper factor, HBZ, interacts with MafB and suppresses transcription through a Maf recognition element. J Cell Biochem. 2010;111:187-94 pubmed publisher
    ..These results suggest a suppressive effect of HBZ on Maf function, which may have a significant role in HTLV-1 related pathogenesis. ..
  19. Ochando I, González Reig S, Ripoll J, Vera A, Martínez Laborda A. Alteration of the shoot radial pattern in Arabidopsis thaliana by a gain-of-function allele of the class III HD-Zip gene INCURVATA4. Int J Dev Biol. 2008;52:953-61 pubmed publisher
    ..In addition, we present results that suggest an interaction between ICU4 function and auxin signaling. ..
  20. Dep ge Fargeix N, Javelle M, Chambrier P, Frangne N, Gerentes D, Perez P, et al. Functional characterization of the HD-ZIP IV transcription factor OCL1 from maize. J Exp Bot. 2011;62:293-305 pubmed publisher
    ..As suggested by the interaction in planta between OCL1 and SWI3C1, a bona fide subunit of the SWI/SNF complex, OCL1 may modulate transcriptional activity of its target genes by interaction with a chromatin remodelling complex...
  21. Magnani E, Barton M. A per-ARNT-sim-like sensor domain uniquely regulates the activity of the homeodomain leucine zipper transcription factor REVOLUTA in Arabidopsis. Plant Cell. 2011;23:567-82 pubmed publisher
    ..This finding, combined with our phylogenetic analysis, suggests that REVOLUTA is the latest type of HD-ZIP III protein to have evolved in land plants. ..
  22. Ciarbelli A, Ciolfi A, Salvucci S, Ruzza V, Possenti M, Carabelli M, et al. The Arabidopsis homeodomain-leucine zipper II gene family: diversity and redundancy. Plant Mol Biol. 2008;68:465-78 pubmed publisher
  23. Mukherjee K, Brocchieri L, Burglin T. A comprehensive classification and evolutionary analysis of plant homeobox genes. Mol Biol Evol. 2009;26:2775-94 pubmed publisher
    ..All 14 homeobox gene classes were represented in flowering plants, Selaginella, and moss, suggesting that they had already differentiated in the last common ancestor of moss and vascular plants. ..
  24. Hamdi H, Bigorgne A, Naveau S, Balian A, Bouchet Delbos L, Cassard Doulcier A, et al. Glucocorticoid-induced leucine zipper: A key protein in the sensitization of monocytes to lipopolysaccharide in alcoholic hepatitis. Hepatology. 2007;46:1986-92 pubmed
    ..GCs enhance GILZ expression, abrogating macrophage sensitivity to LPS and proinflammatory cytokine secretion. These findings may explain the beneficial effect of GC treatment in patients with severe AH. ..
  25. Zanetti M, Chan R, Godoy A, Gonzalez D, Casalongué C. Homeodomain-leucine zipper proteins interact with a plant homologue of the transcriptional co-activator multiprotein bridging factor 1. J Biochem Mol Biol. 2004;37:320-4 pubmed
    ..Upon binding, StMBF1 increases the DNA binding affinity of Hahb-4, and of another plant homeodomain containing protein from the GL2/Hd-Zip IV family, HAHR-1. The biological role of interactions is discussed in this paper. ..
  26. Matsumoto J, Ohshima T, Isono O, Shimotohno K. HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein. Oncogene. 2005;24:1001-10 pubmed
    ..These results suggest dual effects of HBZ on the suppression of AP-1 activity by inhibiting c-Jun function, which may contribute to the dysregulation of cell proliferation. ..
  27. Tron A, Welchen E, Gonzalez D. Engineering the loop region of a homeodomain-leucine zipper protein promotes efficient binding to a monomeric DNA binding site. Biochemistry. 2004;43:15845-51 pubmed
    ..We conclude that the loop located between helix I and helix II of the HD must be regarded as one of the segments that contribute to the present-day diversity in the properties of different HDs. ..
  28. Saito R, Tabata Y, Muto A, Arai K, Watanabe S. Melk-like kinase plays a role in hematopoiesis in the zebra fish. Mol Cell Biol. 2005;25:6682-93 pubmed
    ..Taken together, our data suggest that the zMelk-like gene may play a role in primitive hematopoiesis by affecting the expression of genes critical for hematopoiesis. ..
  29. Zhao Y, Zhou Y, Jiang H, Li X, Gan D, Peng X, et al. Systematic analysis of sequences and expression patterns of drought-responsive members of the HD-Zip gene family in maize. PLoS ONE. 2011;6:e28488 pubmed publisher
    ..Our results reveal a comprehensive overview of the maize HD-Zip gene family and provide the first step towards the selection of Zmhdz genes for cloning and functional research to uncover their roles in maize growth and development. ..
  30. Wu R, Li S, He S, Wassmann F, Yu C, Qin G, et al. CFL1, a WW domain protein, regulates cuticle development by modulating the function of HDG1, a class IV homeodomain transcription factor, in rice and Arabidopsis. Plant Cell. 2011;23:3392-411 pubmed publisher
    ..Our results suggest that rice and Arabidopsis CFL1 negatively regulate cuticle development by affecting the function of HDG1, which regulates the downstream genes BDG and FDH. ..
  31. Chae W, Henegariu O, Lee S, Bothwell A. The mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cells. Proc Natl Acad Sci U S A. 2006;103:9631-6 pubmed
    ..Taken together, our results provide insight into the mechanism that controls autoimmune diseases via the deletion of this single glutamic acid residue in the leucine-zipper domain of Foxp3. ..
  32. Wang Y, Wang J, Li G. Leucine zipper-like domain is required for tumor suppressor ING2-mediated nucleotide excision repair and apoptosis. FEBS Lett. 2006;580:3787-93 pubmed
  33. Given A, Ogut O, Brozovich F. MYPT1 mutants demonstrate the importance of aa 888-928 for the interaction with PKGIalpha. Am J Physiol Cell Physiol. 2007;292:C432-9 pubmed
    ..These results suggest that, during cGMP-mediated signaling, aa 888-928 of MYPT1 mediate the PKGIalpha-MYPT1 interaction. ..
  34. Lopes J, Torgerson T, Schubert L, Anover S, Ocheltree E, Ochs H, et al. Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J Immunol. 2006;177:3133-42 pubmed
    ..Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance. ..
  35. Arce A, Raineri J, Capella M, Cabello J, Chan R. Uncharacterized conserved motifs outside the HD-Zip domain in HD-Zip subfamily I transcription factors; a potential source of functional diversity. BMC Plant Biol. 2011;11:42 pubmed publisher
  36. Oliveria S, Dell Acqua M, Sather W. AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2+ channel activity and nuclear signaling. Neuron. 2007;55:261-75 pubmed
    ..Additionally, activation of the transcription factor NFATc4 via local Ca2+ influx through L-type channels requires AKAP79/150, suggesting that this signaling complex promotes neuronal L channel signaling to the nucleus through NFATc4. ..
  37. Ariel F, Manavella P, Dezar C, Chan R. The true story of the HD-Zip family. Trends Plant Sci. 2007;12:419-26 pubmed
    ..Here, we review recent data for this family of transcription factors from a wide variety of plant species to unravel their crucial role in plant development. ..
  38. Lee E, Hayes D, Langsetmo K, Sundberg E, Tao T. Interactions between the leucine-zipper motif of cGMP-dependent protein kinase and the C-terminal region of the targeting subunit of myosin light chain phosphatase. J Mol Biol. 2007;373:1198-212 pubmed
    ..These results provide rationalization of some of the findings by others using alternative binding analyses. ..
  39. Xie Y, Lee O, Nedumaran B, Seong H, Lee K, Ha H, et al. SMILE, a new orphan nuclear receptor SHP-interacting protein, regulates SHP-repressed estrogen receptor transactivation. Biochem J. 2008;416:463-73 pubmed publisher
    ..Collectively, these results indicate that SMILE isoforms regulate the inhibition of ER transactivation by SHP in a cell-type-specific manner and act as a novel transcriptional co-regulator in ER signalling. ..
  40. Itoh J, Hibara K, Sato Y, Nagato Y. Developmental role and auxin responsiveness of Class III homeodomain leucine zipper gene family members in rice. Plant Physiol. 2008;147:1960-75 pubmed publisher
    ..In addition, some Class III HD-Zip genes may regulate the leaf initiation process in the SAM in an auxin-dependent manner. ..
  41. Zúñiga Mayo V, Marsch Martinez N, de Folter S. JAIBA, a class-II HD-ZIP transcription factor involved in the regulation of meristematic activity, and important for correct gynoecium and fruit development in Arabidopsis. Plant J. 2012;71:314-26 pubmed publisher
  42. Sakuma S, Pourkheirandish M, Matsumoto T, Koba T, Komatsuda T. Duplication of a well-conserved homeodomain-leucine zipper transcription factor gene in barley generates a copy with more specific functions. Funct Integr Genomics. 2010;10:123-33 pubmed publisher
    ..HvHox2 was expressed in all organs examined but Vrs1 was predominantly expressed in immature inflorescence. ..
  43. Grigoryan G, Reinke A, Keating A. Design of protein-interaction specificity gives selective bZIP-binding peptides. Nature. 2009;458:859-64 pubmed publisher
  44. Tahir M, Belmonte M, Elhiti M, Flood H, Stasolla C. Identification and characterization of PgHZ1, a novel homeodomain leucine-zipper gene isolated from white spruce (Picea glauca) tissue. Plant Physiol Biochem. 2008;46:1031-9 pubmed publisher
    ..Overall these data support the notion that PgHZ1 confers hypersensitivity to ABA and that proper expression of this gene may be required for proper embryonic growth. ..
  45. Sharma A, Zhou G, Kupferman J, Surks H, Christensen E, Chou J, et al. Probing the interaction between the coiled coil leucine zipper of cGMP-dependent protein kinase Ialpha and the C terminus of the myosin binding subunit of the myosin light chain phosphatase. J Biol Chem. 2008;283:32860-9 pubmed publisher
    ..Taken together these data support a role for the LZ domain of PKG-Ialpha and the CC domain of MBS in this requisite contractile complex. ..
  46. Komatsuda T, Pourkheirandish M, He C, Azhaguvel P, Kanamori H, Perovic D, et al. Six-rowed barley originated from a mutation in a homeodomain-leucine zipper I-class homeobox gene. Proc Natl Acad Sci U S A. 2007;104:1424-9 pubmed
    ..Phylogenetic analysis demonstrated that the six-rowed phenotype originated repeatedly, at different times and in different regions, through independent mutations of Vrs1. ..
  47. Acharya A, Rishi V, Vinson C. Stability of 100 homo and heterotypic coiled-coil a-a' pairs for ten amino acids (A, L, I, V, N, K, S, T, E, and R). Biochemistry. 2006;45:11324-32 pubmed
    ..In contrast, the a-a' pairs containing charged amino acids (K, R, and E) show the least range in coupling energies and promiscuously encourage heterodimerization. ..
  48. Mason J, Schmitz M, Müller K, Arndt K. Semirational design of Jun-Fos coiled coils with increased affinity: Universal implications for leucine zipper prediction and design. Proc Natl Acad Sci U S A. 2006;103:8989-94 pubmed
    ..Indeed, in applying the algorithm to these 59(2) bZIP interactions, we were able to correctly identify 92% of all strong interactions and 92% of all noninteracting pairs. ..
  49. Mukherjee K, Burglin T. MEKHLA, a novel domain with similarity to PAS domains, is fused to plant homeodomain-leucine zipper III proteins. Plant Physiol. 2006;140:1142-50 pubmed
    ..It is involved in light, oxygen, and redox potential sensation. The fact that HD-ZIP III proteins are transcription factors that have this sensory domain attached to their C terminus uncovers a potential new signaling pathway in plants. ..
  50. Floyd S, Zalewski C, Bowman J. Evolution of class III homeodomain-leucine zipper genes in streptophytes. Genetics. 2006;173:373-88 pubmed publisher
    ..Modification of expression patterns that accompanied diversification of class III HD-Zip genes likely played an important role in the evolution of land plant form...
  51. Tron A, Comelli R, Gonzalez D. Structure of homeodomain-leucine zipper/DNA complexes studied using hydroxyl radical cleavage of DNA and methylation interference. Biochemistry. 2005;44:16796-803 pubmed
    ..The results show that the structure of the complex formed by HD-Zip proteins with DNA is dependent upon both protein intrinsic characteristics and the nucleotides present at the central position of the recognition sequence. ..
  52. Green K, Prigge M, Katzman R, Clark S. CORONA, a member of the class III homeodomain leucine zipper gene family in Arabidopsis, regulates stem cell specification and organogenesis. Plant Cell. 2005;17:691-704 pubmed
    ..We propose that CNA functions in parallel to the CLV loci to promote organ formation. ..
  53. Zhang S, Ma C, Chalfie M. Combinatorial marking of cells and organelles with reconstituted fluorescent proteins. Cell. 2004;119:137-44 pubmed
    ..Furthermore, when one partial GFP polypeptide is fused with a subcellularly localized protein or peptide, this restricted expression leads to the fluorescent marking of cellular components in a subset of cells. ..