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Rajendra K. Agrawal, Ph.D.

Rajendra K. Agrawal, Ph.D.

Director, Division of Translational Medicine, Wadsworth Center
Professor, Department of Biomedical Sciences, University at Albany
Ph.D., Banaras Hindu University, India
Postdoctoral training: Wadsworth Center
(518) 486-5797
Fax: 
(518) 474-5049

Research Interests

Structure and Function of Cell’s Protein-Synthesizing “Machine”

The Agrawal laboratory is engaged in studies of the mechanism of protein-synthesis, or gene translation, in humans and in pathogenic bacteria. Ribosomes, which lie at the center of the protein sysnthesis machinery, conduct protein synthesis in all organism. While the bacterial ribosomes are the major targets of antibiotics, defects in human mitochondrial ribosomes (mitoribosomes) and translation cause multiple devastating genetic diseases. Ribosomes interact with messenger RNA (mRNA), transfer RNAs, and number of protein factors, to facilitate translation. A deep understanding of ribosome structure and function in humans and pathogenic bacteria is necessary for designing or identifying drug targets so that safer drugs can be designed without affecting the human translational machinery. The Agrawal lab’s emphasis is on (i) human mitochondrial, and (ii) mycobacterial ribosomes. His lab uses biochemical, molecular biology, and high-resolution cryo-electron microscopy (cryo-EM) techniques to study these biological systems.

Human mitochondrial ribosomes (mitoribosomes) synthesize specific sets of proteins required by the eukaryotic cell, including components of protein complexes, crucial for generating ~90% of energy (ATP) for the cell. These ribosomes possess a number of novel features. For example, most 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. In addition, most of the ribosome-binding mitochondrial translational factors possess unique amino-acid segments. The goal of studies in the Agrawal lab include the elucidation of mechanisms by which (i) leaderless mRNAs are recruited to the ribosomes, and (ii) unique component ribosomal proteins and translational factors participate in the process of mitochondrial protein synthesis. His lab was first do determine the structure of a mammalian mitochondrial ribosome.

To study mycobacterial protein synthesis, the Agrawal lab collaborates with other Wadsworth investigators, including Drs. Keith Derbyshire, Todd Gray, Joseph Wade, Anil Ojha and Pallavi Ghosh. In collaboration with the Ojha lab, his lab was first to determine structure of an alternative form of mycobacterial ribosome, revealing unique features of mycobacterial ribosome hibernation that has implications in mycobacterial dormancy and drug resistance.

Studies in the Agrawal lab allow him to track conformational transitions undergone by the ribosome and its ligands during protein synthesis. Knowledge of specific conformational transitions 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 to inhibit such transitions. Comparison of results obtained for the bacterial ribosome complexes with those for the host cytosolic and mitochondrial ribosome complexes provides useful information that can lead to identification of new drug targets.

Select Publications

Koripella RK, Sharma MR, Bhargava K, Datta PP, Kaushal PS, Keshavan P, Spremulli LL, Banavali NK, and Agrawal RK.
Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of mitochondrial translation elongation.
Nature Comm.
(2020)
11
(1):
3830.
DOI: 10.1038/s41467-020-17715-2
Koripella RK, Sharma MR, Risteff P, Keshavan P, Agrawal RK.
Structural insights into unique features of the human mitochondrial ribosome recycling.
Proc Natl Acad Sci U S A.
(2019)
116
(17):
8283-8288.
DOI: 10.1073/pnas.1815675116
Koripella RK, Sharma MR, Haque ME, Risteff P, Spremulli LL, Agrawal RK.
Structure of Human Mitochondrial Translation Initiation Factor 3 Bound to the Small Ribosomal Subunit.
iScience.
(2019)
Feb 22
(12):
76–86.
DOI: 10.1016/j.isci.2018.12.030
Li Y, Sharma MR, Koripella RK, Yang Y, Kaushal PS, Lin Q, Wade JT, Gray TA, Derbyshire KM, Agrawal RK, Ojha AK.
Zinc depletion induces ribosome hibernation in mycobacteria.
Proc Natl Acad Sci U S A.
(2018)
115
(32):
8191-8196.
DOI: 10.1073/pnas.1804555115
Shaikh TR, Yassin AS, Lu Z, Barnard D, Meng X, Lu TM, Wagenknecht T, Agrawal RK.
Initial bridges between two ribosomal subunits are formed within 9.4 milliseconds, as studied by time-resolved cryo-EM.
Proc Natl Acad Sci U S A.
(2014)
111
(27):
9822-7.
DOI: 10.1073/pnas.1406744111
Sharma MR, Koc EC, Datta PP, Booth TM, Spremulli LL, Agrawal RK.
Structure of the mammalian mitochondrial ribosomes reveals an expanded functional role for its component proteins.
Cell.
(2003)
115
(1):
97-108.
DOI: 10.1016/s0092-8674(03)00762-1
Frank J, Agrawal RK.
A ratchet-like inter-subunit reorganization of the ribosome during translocation.
Nature.
(2000)
406
(6793):
318-322.
DOI: 10.1038/35018597