Research

  • Thursday, August 15, 2013

    The initiation of mammalian protein synthesis and mRNA scanning mechanism

    Lomakin, I., Steitz, T.A. (2013) Nature 500: 307-311.

    PubMed
  • Thursday, May 9, 2013

    The mechanism of E. coli RNA polymerase regulation by ppGpp is suggested by the structure of their complex

    Zuo, Y., Wang, Y., Steitz, T.A. (2013) Mol Cell 50: 430-436.

    PubMed
  • Friday, February 1, 2013

    Crystal structure of an intermediate of rotating dimers within the synaptic tetramer of the G-segment invertase

    Ritacco, C.J., Kamtekar, S., Wang, J., Steitz, T.A. (2013) Nucleic Acids Res 41(4): 2673-82.

    PubMed
  • Friday, October 12, 2012

    The Hexameric Helicase DnaB Adopts a Nonplanar Conformation during Translocation

    Itsathitphaisarn, O., Wing, R.A., Eliason, W.K., Wang, J., Steitz, T.A. (2012) Cell 151: 267-277.

    PubMed
  • Friday, March 16, 2012

    Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome

    Gagnon, M.G., Seetharaman, S.V., Bulkley, D., Steitz, T.A. (2012) Science 335: 1370-1372.

    PubMed
  • Friday, November 12, 2010

    How the CCA-adding enzyme selects adenine over cytosine at position 76 of tRNA

    Pan, B., Xiong, Y., Steitz, T.A. (2010) Science 330: 937-940.

    PubMed
  • Friday, December 4, 2009

    Structural insight into nascent polypeptide chain-mediated translational stalling

    Seidelt, B., Innis, C.A., Wilson, D.N., Gartmann, M., Armache, J.P., Villa, E., Trabuco, L.G., Becker, T., Mielke, T., Schulten, K., Steitz, T.A., Beckmann, R. (2009) Science 326: 1412-1415.

    PubMed
  • Friday, October 30, 2009

    Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome

    Blaha, G., Stanley, R.E., Steitz, T.A. (2009)Science 325: 966-970.

    PubMed
  • Wednesday, October 7, 2009

    The Nobel Prize in Chemistry 2009

    “for studies of the structure and function of the ribosome.”
    - Nobelprize.org
    - Information for the Public
    -
    Scientific Background

  • Friday, July 17, 2009

    The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation

    Palioura, S., Sherrer, R.L., Steitz, T.A., Soll, D., Simonovic, M. (2009) Science 325: 321-325.

    PubMed
  • Friday, October 24, 2008

    The structure of a transcribing T7 RNA polymerase in transition from initiation to elongation

    Durniak, K.J., Bailey, S. & Steitz, T.A. (2008) Science 322: 553-7.

    PubMed
  • Friday, October 17, 2008

    Insights into the replisome from the structure of a ternary complex of the DNA polymerase III alpha-subunit

    Wing, R.A., Bailey, S. & Steitz, T.A. (2008)J. Mol Biol382: 859-69.

    PubMed
  • Friday, October 19, 2007

    Structure of hexameric DnaB helicase and its complex with a domain of DnaG primase

    Bailey, S., Eliason, W.K. & Steitz, T.A. (2009) Science 318: 459-63.

    PubMed
  • Wednesday, July 25, 2007

    Structures of phi29 DNA polymerase complexed with substrate: the mechanism of translocation in B-family polymerases

    Berman, A.J., Kamtekar, S., Goodman, J.L., Lazaro, J.M., de Vega, M., Blanco, L., Salas, M. & Steitz, T.A. (2007) EMBO Journal 26: 3494-505.

    PubMed
  • Friday, September 8, 2006

    The structure of T. aquaticus DNA polymerase III is distinct from eukaryotic replicative DNA polymerases

    Bailey, S., Wing, R.A. & Steitz, T.A. (2006) Cell 126: 893-904.

    PubMed
  • Wednesday, March 22, 2006

    The phi29 DNA polymerase:protein-primer structure suggests a model for the initiation to elongation transition

    Kamtekar, S., Berman, A.J., Wang, J., Lazaro, J.M., de Vega, M., Blanco, L., Salas, M. & Steitz, T.A. (2006) EMBO Journal 25: 1335-43.

    PubMed
  • Thursday, November 24, 2005

    An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA

    Schmeing, T.M., Huang, K.S., Strobel, S.A. & Steitz, T.A. (2005) Nature 438: 520-4.

    PubMed
  • Friday, November 11, 2005

    Structural insights into the roles of water and the 2' hydroxyl of the P site tRNA in the peptidyl transferase reaction

    Schmeing, T.M., Huang, K.S., Kitchen, D.E., Strobel, S.A. & Steitz, T.A. (2005) Mol Cell 20: 437-48.

    PubMed
  • Friday, August 19, 2005

    Structure of a synaptic gammadelta resolvase tetramer covalently linked to two cleaved DNAs

    Li, W., Kamtekar, S., Xiong, Y., Sarkis, G.J., Grindley, N.D. & Steitz, T.A. (2005) Science 309: 1210-5.

    PubMed
  • Friday, April 22, 2005

    Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance

    Tu, D., Blaha, G., Moore, P.B. & Steitz, T.A. (2005) Cell 121: 257-70.

    PubMed
  • Thursday, August 5, 2004

    Mechanism of transfer RNA maturation by CCA-adding enzyme without using an oligonucleotide template

    Xiong, Y. & Steitz, T.A. (2004) Nature 430: 640-5.

    PubMed
  • Friday, February 6, 2004

    The structural mechanism of translocation and helicase activity in T7 RNA polymerase

    Yin, Y.W. & Steitz, T.A. (2004) Cell 116: 393-404.

    PubMed
  • Saturday, November 1, 2003

    Structures of deacylated tRNA mimics bound to the E site of the large ribosomal subunit

    Schmeing, T.M., Moore, P.B. & Steitz, T.A. (2003) RNA 9: 1345-52.

    PubMed
  • Friday, July 25, 2003

    Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit

    Hansen, J.L., Moore, P.B. & Steitz, T.A. (2003) J Mol Biol 330: 1061-75.

    PubMed
  • Friday, November 15, 2002

    Structural basis for the transition from initiation to elongation transcription in T7 RNA polymerase

    Yin, Y.W. & Steitz, T.A. (2002) Science 298: 1387-95.

    PubMed
  • Tuesday, September 3, 2002

    Structural insights into peptide bond formation

    Hansen, J.L., Schmeing, T.M., Moore, P.B. & Steitz, T.A. (2002) Proc Natl Acad Sci U S A 99: 11670-5.

    PubMed
  • Monday, July 1, 2002

    The structures of four macrolide antibiotics bound to the large ribosomal subunit

    Hansen, J.L., Ippolito, J.A., Ban, N., Nissen, P., Moore, P.B. & Steitz, T.A. (2002) Mol Cell 10: 117-28.

    PubMed
  • Friday, March 1, 2002

    A pre-translocational intermediate in protein synthesis observed in crystals of enzymatically active 50S subunits

    Schmeing, T.M., Seila, A.C., Hansen, J.L., Freeborn, B., Soukup, J.K., Scaringe, S.A., Strobel, S.A., Moore, P.B. & Steitz, T.A. (2002) Nat Struct Biol 9: 225-30.

    PubMed
  • Wednesday, August 1, 2001

    The kink-turn: a new RNA secondary structure motif

    Klein, D.J., Schmeing, T.M., Moore, P.B. & Steitz, T.A. (2001) EMBO Journal 20: 4214-21.

    PubMed
  • Friday, June 1, 2001

    Structure of the replicating complex of a pol alpha family DNA polymerase

    Franklin, M.C., Wang, J. & Steitz, T.A. (2001) Cell 105: 657-67.

    PubMed
  • Tuesday, April 24, 2001

    RNA tertiary interactions in the large ribosomal subunit: the A-minor motif

    Nissen P, Ippolito JA, Ban N, Moore PB, Steitz TA. (2001) Proc Natl Acad Sci U S A 98: 4899-903.

    PubMed
  • Friday, August 11, 2000

    The structural basis of ribosome activity in peptide bond synthesis

    Nissen, P., Hansen, J., Ban, N., Moore, P.B. & Steitz, T.A. (2000) Science 289: 920-30.

    PubMed
  • Friday, August 11, 2000

    The complete atomic structure of the large ribosomal subunit at 2.4 A resolution

    Ban, N., Nissen, P., Hansen, J., Moore, P.B., Steitz, T.A. (2000) Science 289: 905-20.

    PubMed
  • Friday, December 17, 1999

    Structure of a transcribing T7 RNA polymerase initiation complex

    Cheetham, G.M. & Steitz, T.A.(1999) Science 286: 2305-9.

    PubMed
  • Friday, October 15, 1999

    Building a replisome from interacting pieces: sliding clamp complexed to a peptide from DNA polymerase and a polymerase editing complex

    Shamoo, Y. & Steitz, T.A. (1999) Cell 99: 155-66.

    PubMed
  • Thursday, August 26, 1999

    Placement of protein and RNA structures into a 5 A-resolution map of the 50S ribosomal subunit

    Ban, N., Nissen, P., Hansen, J., Capel, M., Moore, P.B. & Steitz, T.A. (1999) Nature 400: 841-7.

    PubMed
  • Friday, August 13, 1999

    Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin

    Silvian, L.F., Wang, J. & Steitz, T.A. (1999) Science 285: 1074-7.

    PubMed
  • Thursday, May 6, 1999

    Structural basis for initiation of transcription from an RNA polymerase-promoter complex

    Cheetham, G.M., Jeruzalmi, D. & Steitz, T.A. (1999) Nature 399: 80-3.

    PubMed
  • Friday, June 26, 1998

    A 9 A resolution X-ray crystallographic map of the large ribosomal subunit

    Ban, N., Freeborn, B., Nissen, P., Penczek, P., Grassucci, R.A., Sweet, R., Frank, J., Moore, P.B. & Steitz, T.A. (1998) Cell 93: 1105-15.

    PubMed
  • Friday, June 27, 1997

    Crystal structure of a pol alpha family replication DNA polymerase from bacteriophage RB69

    Wang, J., Sattar, A.K., Wang, C.C., Karam, J.D., Konigsberg, W.H. & Steitz, T.A. (1997) Cell 89: 1087-99.

    PubMed
  • Thursday, July 18, 1996

    Structure of Taq polymerase with DNA at the polymerase active site

    Eom, S.H., Wang, J. & Steitz, T.A. (1996) Nature 382: 278-81.

    PubMed
  • Friday, July 28, 1995

    Crystal structure of the site-specific recombinase gamma delta resolvase complexed with a 34 bp cleavage site

    Yang, W. & Steitz, T.A. (1995) Cell 82: 193-207.

    PubMed
  • Friday, June 23, 1995

    Crystal structure of lac repressor core tetramer and its implications for DNA looping

    Friedman, A.M., Fischmann, T.O. & Steitz, T.A. (1995) Science 268: 1721-7.

    PubMed
  • Friday, April 16, 1993

    Structure of DNA polymerase I Klenow fragment bound to duplex DNA

    Beese, L.S., Derbyshire, V. & Steitz, T.A. (1993) Science 260: 352-355.

    PubMed
  • Friday, June 26, 1992

    Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor

    Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256: 1783-90.

    PubMed
  • Thursday, January 23, 1992

    Structure of the recA protein-ADP complex

    Story, R.M. & Steitz, T.A. (1992) Nature 355: 374-6.

    PubMed
  • Thursday, January 23, 1992

    The structure of the E. coli recA protein monomer and polymer

    (1992) Nature 355: 318-25.

    PubMed
  • Friday, August 30, 1991

    Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees

    Schultz, S.C., Shields, G.C. & Steitz, T.A. (1991) Science 253: 1001-7.

    PubMed
  • Thursday, July 18, 1991

    Structural basis of anticodon loop recognition by glutaminyl-tRNA synthetase

    Rould, M.A., Perona, J.J. & Steitz, T.A. (1991) Nature 352: 213-8.

    PubMed
  • Thursday, January 10, 1991

    Structural basis for the 3'-5' exonuclease activity of Escherichia coli DNA polymerase I: a two metal ion mechanism

    Beese, L.S. & Steitz, T.A. (1991) EMBO Journal 10: 25-33.

    PubMed
  • Friday, December 1, 1989

    Structure of E. coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP at 2.8 A resolution

    Rould, M.A., Perona, J.J., Soll, D. & Steitz, T.A. (1989) Science 246: 1135-42.

    PubMed
  • Friday, April 8, 1988

    Genetic and crystallographic studies of the 3'-5' exonucleolytic site of DNA polymerase I

    Derbyshire, V., Freemont, P.S., Sanderson, M.R., Beese, L., Friedman, J.M., Joyce, C.M. & Steitz, T.A. (1988) Science 240: 199-201.

    PubMed
  • Thursday, February 28, 1985

    Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP

    Ollis, D., Brick, P., Hamlin, R., Xuong, N.G. & Steitz, T.A. (1985) Nature 313: 762-766.

    PubMed
  • Thursday, April 30, 1981

    Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA

    McKay, D.B. & Steitz, T.A. (1981) Nature 290: 744-9.

    PubMed

The Central Dogma, One Molecule at a T​ime

Our general goal is to understand the biological functions of macromolecules in terms of their detailed molecular structure. Of particular interest are the molecular mechanisms by which those proteins and nucleic acids involved in the central dogma of molecular biology (DNA replication, transcription, translation and genetic recombination) achieve their biological function. Virtually all aspects of the maintenance, rearrangement and expression of information stored in the genome involve interactions between proteins and nucleic acids.

Our recent accomplishments have included the determination of the atomic structure of the 50S ribosomal subunit and its complexes with substrate, intermediate and product analogues as well as complexes with about two dozen antibiotics. These structures establish that the ribosome is a ribozyme, provide insights into the mechanism of peptide bond formation and show how several classes of antibiotics function. We are now obtaining structures of the 70S ribosome captured in various states and including protein factors. In the area of transcription, six structures of T7 RNA polymerase captured in various functional states show the structural basis of the transition from the initiation to elongation phase, which involves a large protein structural rearrangement. They explain the basis of promoter clearance, processivity of the elongation phase, translocation and strand separation. The structures of the CCA-adding enzyme captured in each state of CCA incorporation onto tRNA explain the enzyme’s specificity for nucleotide incorporation in the absence of a nucleic acid template. The structure of a recombination intermediate of γδ resolvase suggests that site specific recombination by this enzyme is achieved by subunit rotation. Insights into the structural basis of DNA replication are emerging from our structures of the Pol III DNA polymerase as well as that of the phage φ29 DNA polymerase in complexes with substrates and with the priming protein. Also, the first structures of the primasome containing the helicase and a fragment of the primase provide a model for primasome function.

Future directions will focus on the complex macromolecular assemblies that are the functional machines in these processes, including the ribosome and the replisome. For example, we wish to establish the atomic structures of the ribosome captured in the act of protein synthesis in each of its conformational states with elongation factors as well as interacting with the proteins involved in protein secretion. Likewise, a mechanistic understanding of replication and recombination will require structures of the assemblies in each step of their functioning. Hypotheses arising from these structures will be tested using site directed mutagenesis and biochemical studies to relate structure to function.

Selected Publications

Zuo, Y., Steitz, T.A. (2015). Crystal structures of the E. coli transcription initiation complexes with a complete bubble. Mol Cell 58(3), 534-540. PubMed

Lin, J., Gagnon, M.G., Bulkley, D., Steitz, T.A. (2015). Conformational changes of elongation factor G on the ribosome during tRNA translocation. Cell 160, 219-227.PubMed

Gagnon, M.G., Lin, J., Bulkley, D., Steitz, T.A. (2014). Crystal structure of elongation factor 4 bound to a clockwise ratcheted ribosome. Science 345, 684-687. PubMed

Lomakin, I., Steitz, T.A. (2013). The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature 500, 307-311. PubMed

Zuo, Y., Wang, Y., Steitz, T.A. (2013). The mechanism of E. coli RNA polymerase regulation by ppGpp is suggested by the structure of their complex. Mol Cell 50(3), 430-436. PubMed

Polikanov, Y.I., Blaha, G.M. Steitz, T.A. (2012). How Hibernation Factors RMF, HPF, and YfiA Turn Off Protein Synthesis Science 336, 915-918. PubMed

Itsathitphaisarn, O., Wing, R.A., Eliason, W.K., Wang, J., Steitz, T.A. (2012). The Hexameric Helicase DnaB Adopts a Nonplanar Conformation during Translocation. Cell 151, 267-277. PubMed

Gagnon, M.G., Seetharaman, S.V., Bulkley, D., Steitz, T.A. (2012). Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science 335, 1370-1372. PubMed

Mitton-Fry, R.M., DeGregorio, S.J., Wang, J., Steitz, T.A., Steitz, J.A. (2010). Poly(A) tail recognition by a viral RNA element through assembly of a triple helix. Science 330, 1244-1247. PubMed

Pan, B., Xiong, Y., Steitz, T.A. (2010). How the CCA-adding enzyme selects adenine over cytosine at position 76 of tRNA.Science 330, 937-940. PubMed

Seidelt, B., Innis, C.A., Wilson, D.N., Gartmann, M., Armache, J.P., Villa, E., Trabuco, L.G., Becker, T., Mielke, T., Schulten, K., Steitz, T.A., Beckmann, R. (2009). Structural insight into nascent polypeptide chain-mediated translational stalling.Science 326, 1412-1415. PubMed

Blaha, G., Stanley, R.E., Steitz, T.A. (2009). Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome. Science 325, 966-970. PubMed

Palioura, S., Sherrer, R.L., Steitz, T.A., Soll, D., Simonovic, M. (2009). The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. Science 325, 321-325. PubMed

Durniak, K.J., Bailey, S., Steitz, T.A. (2008). The structure of a transcribing T7 RNA polymerase in transition from initiation to elongation. Science 322, 553-557. PubMed

Bailey, S. Eliason, W.K., Steitz, T.A. (2007). Structure of hexameric DnaB helicase and its complex with a domain of DnaG primase. Science 318, 459-463. PubMed

Lomakin, I.B., Xiong, Y., Steitz, T.A. (2007). The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together. Cell 129, 319-332.PubMed

Bailey, S., Wing, R.A., Steitz, T.A. (2006). The structure of T. aquaticus DNA polymerase III is distinct from eukaryotic replicative DNA polymerases. Cell 126, 893-904. PubMed

Li, W., Kamtekar, S., Xiong, Y., Sarkis, G.J., Grindley, N.D.F., Steitz, T.A. (2005). Structure of a synaptic γδ resolvase tetramer covalently linked to two cleaved DNAs. Science 309, 1210-1215. PubMed

Tu, D., Blaha, G., Moore, P.B., Steitz, T.A. (2005). Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell121, 257-270. PubMed

Schmeing, T.M., Huang, K.S., Strobel, S.A., Steitz, T.A. (2005). An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Nature 438, 520-524. PubMed


A complete list of publications can be found HERE.