Investigators and Program Directors

Research Interests

Structure and Function of Cell’s Protein-Synthesizing “Machine”
My laboratory is engaged in studies of the protein-synthesizing machine, the ribosome, which interacts with messenger RNA (mRNA), transfer RNAs, and a number of protein factors, to facilitate translation of the genetic information encoded by the mRNA into the amino-acid sequence of a protein. In particular, my research explores (i) the structure and function of organellar ribosomes, and (ii) the structural dynamics of ligands that interact with the ribosome during protein synthesis. Biochemical and molecular biology techniques, combined with cryo-electron microscopy and advanced computer image processing methods, are used to determine the three-dimensional structures of the macromolecular complexes at sub-nanometer resolution.

Organellar ribosomes synthesize specific sets of proteins required by the eukaryotic cell. Mitochondrial ribosomes synthesize components of protein complexes crucial in ATP synthesis, while chloroplast ribosomes synthesize proteins that participate in photosynthesis. Both of these organellar ribosomes possess a number of component proteins that are not present in the cytoplasmic ribosomes from the same cells. Certain unique features of the translation process on organellar ribosomes suggest functional roles that could plausibly be filled by such novel components. For example, mammalian mitochondrial mRNAs are leaderless, i.e., they do not possess either the Shine-Dalgarno sequence or the 5’ cap that guide the recruitment of mRNAs to cytoplasmic ribosomes. One of the goals of our studies is to elucidate the mechanism by which leaderless mRNAs are recruited to the mitochondrial ribosome.

Knowledge of specific conformational transitions, undergone by the ribosome and its ligands during protein synthesis, is key to understanding the molecular mechanisms of protein synthesis itself, as well as the actions of antibiotics that target the bacterial ribosome or ribosomal ligands. We are studying the dynamics of single amino-acid residues of ribosomal ligands, in efforts to delineate a number of such transitions.

Contact Information

Phone: (518) 486-5797
Fax: (518) 474-5049
E-mail:agrawal@wadsworth.org