In 2005, Ramakrishnan's laboratory published a 5.5 Angstrom resolution structure of the 30S subunit. The following year, his laboratory determined the complete molecular structure of the 30S subunit of the ribosome and its complexes with several antibiotics. This was followed by studies that provided structural insights into the mechanism that ensures the fidelity of protein biosynthesis. More recently in 2007 his laboratory has determined the atomic structure of the whole ribosome in complex with its tRNA and mRNA ligands. Ramakrishnan is also known for his past work on histone and chromatin structure.
Ramakrishnan is internationally recognised for determination of the atomic structure of the 30S ribosomal subunit. Earlier he mapped the arrangement of proteins in the 30S subunit by neutron diffraction and solved X-ray structures of individual components and their RNA complexes. Fundamental insights came from his crystallographic studies of the complete 30S subunit. The atomic model included over 1500 bases of RNA and 20 associated proteins. The RNA interactions representing the P-sitetRNA and the mRNA binding site were identified and the likely modes of action of many clinically important antibiotics determined. His most recent work goes to the heart of the decoding mechanism showing the 30S subunit complexed with poly-U mRNA and the stem-loop of the cognate phenylalanine tRNA. Anti-codon recognition leaves the "wobble" base free to accommodate certain non-Watson/Crick basepairs, thus providing an atomic description of both codon:anti-codon recognition and "wobble". He has also made substantial contributions to understanding how chromatin is organised, particularly the structure of linker histones and their role in higher order folding.
Ramakrishnan married Vera Rosenberry in 1975, an author and illustrator of children's books. His stepdaughter Tanya Kapka is a doctor in Oregon, and his son Raman Ramakrishnan is a cellist based in New York.
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^Ramakrishnan, V.; Wimberly, Brian T.; Brodersen, Ditlev E.; Clemons, William M.; Morgan-Warren, Robert J.; Carter, Andrew P.; Vonrhein, Clemens; Hartsch, Thomas (2000). "Structure of the 30S ribosomal subunit". Nature407 (6802): 327–339. doi:10.1038/35030006. PMID11014182.
^Ramakrishnan, V.; Carter, Andrew P.; Clemons, William M.; Brodersen, Ditlev E.; Morgan-Warren, Robert J.; Wimberly, Brian T. (2000). "Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics". Nature407 (6802): 340–348. doi:10.1038/35030019. PMID11014183.
^Ramakrishnan, V.; Finch, J. T.; Graziano, V.; Lee, P. L.; Sweet, R. M. (1993). "Crystal structure of globular domain of histone H5 and its implications for nucleosome binding". Nature362 (6417): 219–223. doi:10.1038/362219a0. PMID8384699.
^Ogle, J. M.; Brodersen, DE; Clemons, WM Jr; Tarry, MJ; Carter, AP; Ramakrishnan, V (2001). "Recognition of Cognate Transfer RNA by the 30S Ribosomal Subunit". Science (New York) 292 (5518): 897–902. doi:10.1126/science.1060612. PMID11340196.
^Brodersen, Ditlev E.; Clemons, William M.; Carter, Andrew P.; Morgan-Warren, Robert J.; Wimberly, Brian T.; Ramakrishnan, V. (2000). "The Structural Basis for the Action of the Antibiotics Tetracycline, Pactamycin, and Hygromycin B on the 30S Ribosomal Subunit". Cell103 (7): 1143–1154. doi:10.1016/s0092-8674(00)00216-6. PMID11163189.
^Ogle, James M.; Murphy, Frank V.; Tarry, Michael J.; Ramakrishnan, V. (2002). "Selection of tRNA by the Ribosome Requires a Transition from an Open to a Closed Form". Cell111 (5): 721–732. doi:10.1016/s0092-8674(02)01086-3. PMID12464183.