A Homologue of Eukaryotic Initiation Factor 5A
(eIF-5A)

Eukaryotic initiation factor 5A (eIF-5A) is ubiquitous in eukaryotes and archaebacteria and is essential for cell proliferation and survival. The crystal structure of the eIF-5A homologue (PhoIF-5A) from Pyrococcus horikoshii OT3 was determined by the molecular replacement method. PhoIF-5A is predominantly composed of b-strands comprising two distinct folding domains, an N-domain and a C-domain, connected by a short linker peptide (residues 70-71). The N-domain has an SH3-like barrel, while the C-domain folds in an (oligonucleotide/oligosaccharide binding) OB fold. Several lines of evidence suggest that eIF-5A functions as a biomodular protein capable of interacting with protein and nucleic acid. The surface representation of electrostatic potential shows that PhoIF-5A has a concave surface with positively charged residues between the N- and C-domains. In addition, a flexible long hairpin loop, L1 (residues 33-41), with a hypusine modification site is positively charged, protruding from the N-domain. In contrast, the opposite side of the concave surface at the C-domain is mostly negatively charged. These findings led to the speculation that the concave surface and loop L1 at the N-domain may be involved in RNA binding, while the opposite side of the concave surface in the C-domain may be involved in protein interaction.

Figure Caption A cluster of positively charged residues at the putative RNA-binding region of PhoIF-5A. left: The balls-and-sticks represent positive charged residues that may contribute to RNA binding. right: View rotated 90 degree from left one. References Crystal Structure of Hyperthermophilic Archaeal Initiation Factor 5A: A Homologue of Eukaryotic Initiation Factor 5A (eIF-5A) Min Yao, Akiko Ohsawa, Shingo Kikukawa, Isao Tanaka and Makoto Kimura J. Biochem.(ToKyo), 133, 75-81 (2003)