��������Ϸ��վ

On 21st July 1932, on a farm in Nebraska, Audrey Stevens was born. One of the proteins she isolated during her career would be named after her and in 2001, only nine years before her death, its three dimensional structure would be determined.

Audrey Stevens is one of four researchers credited with the discovery of RNA polymerase- the enzyme which transcribes DNA into RNA - but she also studied some of the proteins that specify which genes are transcribed. Proteins called sigma factors direct RNA polymerase to specific genes. In the bacterium Escherichia coli, a sigma factor called sigma70 (σ⁷⁰) directs the polymerase to transcribe many of the ‘housekeeping�� genes - those which are needed in the everyday life of the cell.

In 1972, Stevens published a described the isolation of a 10 kDa protein which was associated with RNA polymerase after E.coli was infected with T4 bacteriophage. Further work showed that this protein, which comes from the bacteriophage, bound to σ⁷⁰ and inhibited its function. The gene encoding this protein was identified in 1993 by who named the protein “Audrey Stevens�� Inhibitor��

The structure of Audrey Stevens�� Inhibitor was determined by NMR and published by two groups in late 2001 () and early 2002 (). It is a bundle of seven alpha helices, and forms a dimer in solution. The image to the left shows the structure in cartoon representation with each monomer coloured in a different shade of green. When determined, the fold of the protein was new to the PDB archive, and indeed a search using shows there remain few close structural homologues in the archive today.

Audrey Stevens�� Inhibitor is made early on in the cycle of replication for the T4 bacteriophage, it binds to E.coli σ⁷⁰, preventing the bacterium from expressing many of its ‘housekeeping genes�� and thus freeing the polymerase to preferentially make T4 mRNA, and therefore T4 protein.

While a dimer in solution, a further structure of Audrey Stevens�� Inhibitor bound to a peptide from σ⁷⁰ ( showed that Audrey Stevens�� Inhibitor binds to σ⁷⁰ with residues which are buried in the dimer interface, so the dimer must dissociate in order to inhibit σ⁷⁰.  When Audrey Stevens' Inhibitor and σ⁷⁰ interact, the DNA-binding surface of σ⁷⁰ becomes buried, preventing it recognising the promoters of target genes. The image above shows Audrey Stevens' inhibitor in green cartoons bound to C‐terminal conserved region 4 peptide of σ⁷⁰  shown in purple.

In 1998, Stevens was elected a member of the US National Academy of Sciences. Find out more about Audrey Stevens in and see all the in the PDB archive on PDBe's pages