The shape of the DNA minor groove directs binding by the DNA-bending protein Fis

TY - JOUR

T1 - The shape of the DNA minor groove directs binding by the DNA-bending protein Fis

AU - Stella, Stefano

AU - Cascio, Duilio

AU - Johnson, Reid C.

PY - 2010/4/15

Y1 - 2010/4/15

N2 - The bacterial nucleoid-associated protein Fis regulates diverse reactions by bending DNA and through DNAdependent interactions with other control proteins and enzymes. In addition to dynamic nonspecific binding to DNA, Fis forms stable complexes with DNA segments that share little sequence conservation. Here we report the first crystal structures of Fis bound to high- and low-affinity 27-base-pair DNA sites. These 11 structures reveal that Fis selects targets primarily through indirect recognition mechanisms involving the shape of the minor groove and sequence-dependent induced fits over adjacent major groove interfaces. The DNA shows an overall curvature of ∼65° , and the unprecedented close spacing between helix-turn-helix motifs present in the apodimer is accommodated by severe compression of the central minor groove. In silico DNA structure models show that only the roll, twist, and slide parameters are sufficient to reproduce the changes in minor groove widths and recreate the curved Fis-bound DNA structure. Models based on naked DNA structures suggest that Fis initially selects DNA targets with intrinsically narrow minor grooves using the separation between helix-turn-helix motifs in the Fis dimer as a ruler. Then Fis further compresses the minor groove and bends the DNA to generate the bound structure.

AB - The bacterial nucleoid-associated protein Fis regulates diverse reactions by bending DNA and through DNAdependent interactions with other control proteins and enzymes. In addition to dynamic nonspecific binding to DNA, Fis forms stable complexes with DNA segments that share little sequence conservation. Here we report the first crystal structures of Fis bound to high- and low-affinity 27-base-pair DNA sites. These 11 structures reveal that Fis selects targets primarily through indirect recognition mechanisms involving the shape of the minor groove and sequence-dependent induced fits over adjacent major groove interfaces. The DNA shows an overall curvature of ∼65° , and the unprecedented close spacing between helix-turn-helix motifs present in the apodimer is accommodated by severe compression of the central minor groove. In silico DNA structure models show that only the roll, twist, and slide parameters are sufficient to reproduce the changes in minor groove widths and recreate the curved Fis-bound DNA structure. Models based on naked DNA structures suggest that Fis initially selects DNA targets with intrinsically narrow minor grooves using the separation between helix-turn-helix motifs in the Fis dimer as a ruler. Then Fis further compresses the minor groove and bends the DNA to generate the bound structure.

KW - DNA bending

KW - DNA structure

KW - Nucleoid protein

KW - Protein-DNA recognition

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=77950934795&partnerID=8YFLogxK

U2 - 10.1101/gad.1900610

DO - 10.1101/gad.1900610

M3 - Journal article

C2 - 20395367

AN - SCOPUS:77950934795

SN - 0890-9369

VL - 24

SP - 814

EP - 826

JO - Genes & Development

JF - Genes & Development

IS - 8

ER -