Back to Structural Biology Home
One Step Back

Home Page of Prof. Mark Safro

Ph.D., Institute of Crystallography, Academy of Sciences of the USSR, Moscow
The William and Lee Abramowitz Professorial Chair of Molecular Biophysics

telephone: 972-8-9343320
e-mail: mark.safro@weizmann.ac.il




Members of my group:

Dr. Nina Moor, Visiting Scientist
Dr. Naama Kessler, Amit naama.kessler@weizmann.ac.il
Olga Kogan, PhD student olga.kogan@weizmann.ac.il
Gregori Linschiz, PhD student gregory.linschitz@weizmann.ac.il
Inna Solomon, PhD student inna.solomon@weizmann.ac.il
Olga Belenkiy, Rotationolga.belenkiy@weizmann.ac.il
Ester Kitayner, Msc. student



Research projects

X-ray structure analysis of tRNA synthetases and their functional complexes isolated from Thermophilic bacteria

Functional and Structural studies of Eukaryotic aminoacyl - tRNA synthetases.

Structural and functional studies of tRNA-protein complexes

Growth and X-ray structure analysis of crystals of cytoskeletal proteins (in collaboration with B. Geiger)



Biological Crystallography

Aminoacyl-tRNA Synthetase

The atomic structure of heterodimeric (alpha beta)2 Phenylalanyl-tRNA synthetase from Thermus thermophilus (PheRSTT) has been determined by X-ray analysis at 2.9 Å resolution.

The final model includes 1051 amino acid residues, 331 water molecules and a magnesium ion. The alpha beta heterodimer consists of 10 structural domains. Two of them, A1-A2, belong to the alpha-subunit and eight, B1-B, to the beta-subunit.

The 3D structure of PheRSTT reveals that

  1. the specific antiparallel fold in the alpha-subunit is indeed similar to the class II active-site domains;

  2. the beta-subunit contains a "catalytic-like" fold, an anticodon binding fold, an RNA-binding fold with characteristic RNP motifs, and Src-homology 3 (SH3) domain (which is a common feature of signaling eucaryotic proteins);

  3. the beta-subunit plays a crucial role in the alteration of the primary site of aminoacylation; and

  4. the homodimeric and the heterodimeric PheRSTT interfaces have equivalent topology (with M. Delarue and L. Reshetnikova, Institute of Molecular Biology, Moscow).

The structure determination of PheRSTT complexed with cognate tRNAPhe . The crystal structure of PheRS complexed with cognate tRNA has been solved at 3.2A resolution. The interaction of PheRS with tRNA stabilize the flexible N-Terminal part of the alpha-subunit, which appeared to form the enzyme's 11th domain, comprising a coiled- coil structure (helical arm). Anticodon recognition upon tRNA binding is performed by the B8 domain, the structure of which is to that of the RNA-binding domain of the spliceosomal protein U1A. The Th. thermophilus PheRS approaches the anticodon loop from the minor groove side. The tRNAPhe is a newly recognized type of RNA molecule specifically interacting with the RBD fold.

We cloned, sequenced, and expressed human PheRS. The layout of the human sequence indicates that the general tRNA binding mode and anticodon recognition differ between procaryotes and eukaryotes for the phenylalanine system. Northern blot hybridization analysis from malignant and normal human tissues enabled us to assess the relative expression levels of the alpha- and beta- subunits independently, in view of the additional cellular role proposed for the beta-subunit in tumorogenic events. The levels of mRNA corresponding to the alpha- and beta-subunits are remarkably similar in all cell types and tissues examined, thus indicating the implication of the entire heterodimer in tumorogenic events.




Recent publications



(This page was last updated on January, 1999 by Yehudit Weisinger)
Back to Structural Biology Home