Structural basis for DNA bending by the architectural transcription factor LEF-1

Love, John J.; Li, Xiang; Case, David A.; Giese, Klaus; Grosschedl, Rudolf; Wright, Peter E.

doi:10.1038/376791a0

Cited by 578 publications

(618 citation statements)

References 31 publications

Supporting

Mentioning

582

Contrasting

Unclassified

Order By: Relevance

“…In certain cases, such as the complexes of TBP (Kim et al, 1993a,b), SRY (Werner et al, 1995), PurR (Schumacher et al, 1994), and Lef-1 (Love et al, 1995), the DNA bends away from a concave protein surface, and the protein-DNA interfaces are distinguished by intercalation of nonpolar side chains into the DNA (Werner et al, 1996). In other cases, such as the DNA complexes of MATa1/R2 , serum response factor (Pellegrini et al, 1995), CAP (Schultz et al, 1991;Warwicker et al, 1987), and the 434 (Aggarwal et al, 1988) and metJ (Somers & Phillips, 1992) repressors, intercalation is not observed.…”

Section: Dna Bending Results From Neutralization Of Two Tpcmentioning

confidence: 99%

Electrostatic Mechanism for DNA Bending by bZIP Proteins

et al. 1997

View full text Add to dashboard Cite

Biology is replete with examples of protein-induced DNA bending, yet the forces responsible for bending have been neither established nor quantified. Mirzabekov and Rich proposed in 1979 that asymmetric neutralization of the anionic phosphodiester backbone by basic histone proteins could provide a thermodynamic driving force for DNA bending in the nucleosome core particle [Mirzabekov, A. D., & Rich, A. (1979) A. 93, 9515-9520]. Here it is shown that bZIP proteins bend DNA via a mechanism involving direct contacts between one or two basic side chains and a symmetry-related pair of unique, nonbridging phosphate oxygens. The locations of these phosphates provide direct experimental support for a protein-induced bending mechanism based on asymmetric charge neutralization. This straightforward mechanism is compatible with many DNA-recognition motifs and may represent a general strategy for the assembly of protein-DNA complexes of defined stereochemistries.

show abstract

Section: Dna Bending Results From Neutralization Of Two Tpcmentioning

confidence: 99%

Electrostatic Mechanism for DNA Bending by bZIP Proteins

et al. 1997

View full text Add to dashboard Cite

show abstract

“…NIH-PA Author Manuscript NIH-PA Author Manuscript that they may be important characteristics of genetic regulation (e.g., (11,36,37,(59)(60)(61)(62)(63)(64)(65)). In LacI and its homologues, the hinge helix is responsible for both of these features.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Extrinsic Interactions Dominate Helical Propensity in Coupled Binding and Folding of the Lactose Repressor Protein Hinge Helix

2006

View full text Add to dashboard Cite

A significant number of eukaryotic regulatory proteins are predicted to have disordered regions. Many of these proteins bind DNA, which may serve as a template for protein folding. Similar behavior is seen in the prokaryotic LacI/GalR family of proteins that couple hinge-helix folding with DNA binding. These hinge regions form short α-helices when bound to DNA, but appear to be disordered in other states. An intriguing question is whether and to what degree intrinsic helix propensity contributes to the function of these proteins. In addition to its interaction with operator DNA, the LacI hinge helix interacts with the hinge helix of the homodimer partner as well as to the surface of the inducer-binding domain. To explore the hierarchy of these interactions, we made a series of substitutions in the LacI hinge helix at position 52, the only site in the helix that does not interact with DNA and/or the inducer-binding domain. The substitutions at V52 have significant effects on operator binding affinity and specificity, and several substitutions also impair functional communication with the inducer-binding domain. Results suggest that helical propensity of amino acids in the hinge region alone does not dominate function; helix-helix packing interactions appear to also contribute. Further, the data demonstrate that variation in operator sequence can overcome side chain effects on hinge helix folding and/or hinge•hinge interactions. Thus, this system provides a direct example whereby an extrinsic interaction (DNA binding) guides internal events that influence folding and functionality. KeywordsLacI; helical propensity; allostery; DNA binding Protein folding has long been a fundamental issue in biological sciences. Beyond the general question of how a polypeptide sequence adopts a three-dimensional structure, coupled folding and binding have been identified as a key feature of partially unstructured proteins in multiple regulatory processes (e.g., transcription regulation, signal transduction, membrane transport and signaling (6-9)). Indeed, more and more intrinsically disordered proteins are found to fold upon binding to their target partners, ligands, or even small ions (10-13). In the case of transcription regulation, mutual cooperative folding of both protein and DNA has been † This work was supported by NIH Grant GM22441 and Robert A. Welch Grant C-576 to Kathleen Shive Matthews. Liskin Swint-Kruse is supported by NIH Grant P20 RR17708 from the Institutional Development Award program of the National Center for Research Resources.*To whom correspondence should be addressed. Telephone: 713−348−4871; Fax: 713−348−6149; Email: E-mail: ksm@bioc.rice.edu.. observed (6,11,14,15). In this paper, coupled folding is explored in greater detail for the hinge helix of the lactose repressor protein (LacI) 1 . NIH Public AccessLacI is a premier model for the regulation of gene expression and allosteric transition in biological systems (2) 2 . This 150-kDa homotetramer is a dimer of functionally independent dimers, with ...

show abstract

“…The model of the Ste11-DNA complex was obtained via altering the existing Lef-1/DNA NMR model by Love et al (21). Using the modeling program SETOR (33), the helix 1-to-2 loop in the Lef-1 NMR model was shortened by removing amino acids V21 to S24 alike the missing four amino acids in the Ste11 loop.…”

Section: Ste11 Modelingmentioning

confidence: 99%

“…The reported NMR structures of Sry/DNA (20) and Lef-1/DNA (21) complexes have elucidated the nature of the sequence specific-HMG box/DNA interaction. One arm of the L-shape is formed by helix 1 and 2, the second by helix 3 and the adjacent extended C-terminal segment.…”

Section: Introductionmentioning

confidence: 99%

Sequence-specific HMG box factors recognize 10-12 base pair minor groove motifs

Beest

Dooijes

Wetering

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

SummarySequence specific HMG box factors bind and bend DNA via interactions in the minor groove.3D NMR analyses have provided the structural basis for this interaction. The cognate HMG domain DNA motif is generally believed to span 6 to 8 bases. However, alignment of promotor elements controlled by the yeast genes Ste11 and Rox1 has indicated strict conservation of a larger DNA motif. By site selection, we identify a highly specific 12 bp motif for Ste11:AGAACAAAGAAA. Similarly, we show that Tcf1, MatMc and Sox4 bind unique, highly specific DNA motifs of 12, 12 and 10 bp respectively. Footprinting with a deletion mutant of Ste11 reveals a novel interaction between the 3' base pairs of the extended DNA motif and amino acids Cterminal to the HMG domain. The sequence-specific interaction of Ste11 with these 3' base pairs contributes significantly to binding and bending of the DNA motif.

show abstract

Structural basis for DNA bending by the architectural transcription factor LEF-1

Cited by 578 publications

References 31 publications

Electrostatic Mechanism for DNA Bending by bZIP Proteins

Electrostatic Mechanism for DNA Bending by bZIP Proteins

Extrinsic Interactions Dominate Helical Propensity in Coupled Binding and Folding of the Lactose Repressor Protein Hinge Helix

Sequence-specific HMG box factors recognize 10-12 base pair minor groove motifs

Contact Info

Product

Resources

About