PDBsum entry 1fzp

Transcription/DNA

PDB id: 1fzp

Contents

Protein chains

100 a.a. *

105 a.a. *

DNA/RNA

Metals

_CA ×2

* Residue conservation analysis

PDB id:

1fzp

Name:

Transcription/DNA

Title:

Crystal structures of sara: a pleiotropic regulator of virulence genes in s. Aureus

Structure:

5'-d(p Ap Tp Ap Tp Ap Tp A)-3'. Chain: w, k. Engineered: yes. Staphylococcal accessory regulator a. Chain: d, b. Synonym: sara. Engineered: yes

Source:

Synthetic: yes. Staphylococcus aureus. Organism_taxid: 1280. Strain: db. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.95Å R-factor: 0.220 R-free: 0.308

Authors:

M.A.Schumacher,B.Hurlburt,R.G.Brennan

Key ref:

M.A.Schumacher et al. (2001). Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus. Nature, 409, 215-219. PubMed id: 11196648 DOI: 10.1038/35051623

Date:

03-Oct-00 Release date: 22-Jan-01

Protein chain

Q53600  (SARA_STAAU) -

Protein chain

Q53600  (SARA_STAAU) -

DNA/RNA chains

A-T-A-T-A-T-A 7 bases

A-T-A-T-A-T-A 7 bases

DOI no: 10.1038/35051623

Nature 409:215-219 (2001)

PubMed id: 11196648

Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus.

M.A.Schumacher, B.K.Hurlburt, R.G.Brennan.

ABSTRACT

Staphylococcus aureus is a major human pathogen, the potency of which can be attributed to the regulated expression of an impressive array of virulence determinants. A key pleiotropic transcriptional regulator of these virulence factors is SarA, which is encoded by the sar (staphylococcal accessory regulator) locus. SarA was characterized initially as an activator of a second virulence regulatory locus, agr, through its interaction with a series of heptad repeats (AGTTAAG) within the agr promoter. Subsequent DNA-binding studies have revealed that SarA binds readily to multiple AT-rich sequences of variable lengths. Here we describe the crystal structure of SarA and a SarA-DNA complex at resolutions of 2.50 A and 2.95 A, respectively. SarA has a fold consisting of a four-helix core region and 'inducible regions' comprising a beta-hairpin and a carboxy-terminal loop. On binding DNA, the inducible regions undergo marked conformational changes, becoming part of extended and distorted alpha-helices, which encase the DNA. SarA recognizes an AT-rich site in which the DNA is highly overwound and adopts a D-DNA-like conformation by indirect readout. These structures thus provide insight into SarA-mediated transcription regulation.

Selected figure(s)

Figure 1.
Figure 1: The SarA dimer and SarA -DNA complex. a, Views of SarA looking directly into the DNA-binding pocket or from the 'back' side. The secondary structures, -hairpin and C-terminal loop of one monomer are labelled. Each monomer is red or green. b, The SarA -DNA complex in the identical orientation of the corresponding apo SarA directly above. The DNA duplex is shown as CPK atoms, with carbon, nitrogen, oxygen and phosphates coloured white, blue, red and yellow, respectively. The 4B gripper helix of one monomer is also labelled. The narrow and deep minor groove and major groove are seen on the left and right respectively.

Figure 2.
Figure 2: SarA inducible regions. a, Superimposed SarA monomers of the DNA-bound and apo protein. The core region is blue and the inducible regions are yellow and magenta for the apo and DNA bound proteins, respectively. The hinge is labelled. b , Conformational changes induced by DNA binding. The apo form is shown on top (inducible regions in yellow) and the DNA-bound form below (inducible regions in magenta). The DNA duplex and Cys 9 side chains, which line the DNA binding channel, are shown as CPK atoms, with carbon, nitrogen, oxygen and phosphate/sulphur coloured white, blue, red and yellow, respectively.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2001, 409, 215-219) copyright 2001.

Figures were selected by an automated process.