Peter B Moore
Sterling Prof. Chemistry, Prof. Mol Biophys Biochem, Emeritus
We pursue RNA structures both by high field NMR, and by X-ray crystallography, and we are also interested in the structures of proteins that interact with RNAs, and ribonucleoprotein structure. On the NMR side, for example, we are using both homonuclear and heteronuclear approaches to determine the structures of box H/ACA RNAs and the complexes they form with their rRNA substrates. The development of new techniques is also an interest.
On the crystallographic side, we continue to collaborate with Prof. T.A. Steitz on the determination of the three-dimensional structure of the ribosome, the complexes it forms with ligands like antibiotics, and the conformational effects of ribosomal mutations. The object we have been concentrating on is the large ribosomal subunit from the halophilic archaean Haloarcula marismortui, which we solved at a resolution of 2.4 Å in 2000. Efforts are also being made to determine the structure of eukaryotic ribosomes at atomic resolution.
In the 1960s, when molecular biology first emerged as a recognized discipline, only three classes of RNAs were known: rRNAs, tRNAs, and mRNAs. In recent decades, many other kinds of RNAs have been discovered, siRNAs and related regulatory RNAs being only the most recent examples. They all make important contributions to gene expression in one way or another.
Extensive Research Description
By protein standards, our understanding of RNA structure and function is primitive because it was technically difficult to determine RNA structures for many years. Consequently, even though the technical problems have been overcome, there are lots of RNAs—many of them recently discovered—for which we do not have structures, and hence cannot fully explain their functional properties. The Moore group studies RNA structure/function using NMR and X-ray crystallography as well as molecular biological techniques. The structures being investigated today include: 1) those that form when box H/ACA snoRNAs interact with the rRNA sequences they target for pseudouridylation; and 2) the ribosomal proteins/mRNA complexes responsible for the autogenous regulation of ribosomal protein synthesis. We are also trying to identify the sources of the species specificity shown by many of the antibiotics that inhibit ribosome activity by binding to highly conserved rRNA sequences, and to determine the three-dimensional structure of the eukaryotic ribosome.