CRYSTAL-STRUCTURES OF EUKARYOTIC TRANSLATION INITIATION-FACTOR 5A FROM METHANOCOCCUS-JANNASCHII AT 1.8 ANGSTROM RESOLUTION

Eukaryotic translation initiation factor 5A (eIF-5A) is a ubiquitous p rotein found in all eukaryotic cells. The protein is closely associate d with cell proliferation in the G(1)-S stage of the cell cycle. Recen t findings show that the eIF-5A proteins are highly expressed in tumor cells and act as a cofactor of the Rev protein in HIV-1-infected cell s. The mature eIF is the only protein known to have the unusual amino acid hypusine, a post-translationally modified lysine. The crystal str ucture of eIF-5A from Methanococcus jannaschii (MJ eIF-5A) has been de termined at 1.9;Angstrom and 1.8 Angstrom resolution in two crystal fo rms by using the multiple isomorphous replacement method and the multi wavelength anomalous diffraction method for the first crystal form and the molecular replacement method for the second crystal form. The str ucture consists of two folding domains, one of which is similar to the oligonucleotide-binding domain found in the prokaryotic cold shock pr otein and the translation initiation factor IF1 despite the absence of any significant sequence similarities. The 12 highly conserved amino acid residues found among eIF-5As include the hypusine site and form a long protruding loop at one end of the elongated molecule.