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Rajendra K. Agrawal, Ph.D.

Rajendra K. Agrawal, Ph.D.

Deputy 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 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, his lab studies structure and function of human and bacterial ribosomes, with an emphasis on human mitochondrial ribosomes, using biochemical, molecular biology, and high-resolution cryo-electron microscopy (cryo-EM) techniques.  

 

Mitochondrial ribosomes synthesize specific sets of proteins required by the eukaryotic cell, including components of protein complexes crucial in ATP synthesis. These ribosomes possess a number of component proteins that are not present in the cytoplasmic ribosomes from the same cells. Furthermore, several of their homologous proteins possess unique N- or/and C-terminal extensions. Certain unique features of the translation process on organellar ribosomes suggest functional roles that could plausibly be filled by such novel components. 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 Laboratory includes 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 studies 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, 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