Investigators and Program Directors

Research Interests

My laboratory is engaged in studies of the protein synthesizing machinery of the cell, the ribosome. Our particular focus is on two aspects of this machinery:

1. the structure and function of organellar ribosomes; and
2. the structural dynamics of ligands that interact with ribosomes during protein biosynthesis.

Various biochemical and molecular biology techniques, combined with high-resolution cryo-electron microscopy and advanced computer image processing methods, are used to determine the three-dimensional (3D) structures of the ribosome and its functional complexes.

Unlike the level of understanding reached for the bacterial and eukaryotic cytoplasmic ribosomes, very little is known about the structures and functions of organellar ribosomes. The organellar ribosomes synthesize proteins crucial to the eukaryotic cell. For example, mitochondrial ribosomes synthesize proteins involved in the electron-transport system and in apoptosis. Furthermore, two component proteins of the mitochondrial ribosome are directly involved in apoptosis. We have obtained the first 3D maps of the chloroplast and mammalian mitochondrial ribosomes. Studies are underway to identify specific components in the 3D maps of these ribosomes.

During protein biosynthesis, the ribosome interacts with a number of ligands, including initiation factors, mRNAs, tRNAs, and elongation and termination factors. All of these ligands, as well as the ribosome itself, undergo large conformational changes during their interactions. Knowledge of specific conformational transitions is the key to understanding the molecular mechanisms of not only protein biosynthesis but also antibiotic action: some of these structural transitions from one conformational state to another can be blocked by the presence of specific antibiotics. Through the combination of sophisticated techniques noted above, we are studying the dynamics of single amino-acid residues of such ribosomal ligands.

Contact Information

Phone: (518) 486-5797
Fax: (518) 474-7992
E-mail:agrawal@wadsworth.org