Crystal structure of hyperthermophilic archaeal initiation factor 5A: 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 a hyperthermophilic archaebacterium Pyrococcus horikoshii OT3 was determined at 2.0 A resolution by the molecular replacement method. PhoIF-5A is predominantly composed of beta-strands comprising two distinct folding domains, an N-domain (residues 1-69) and a C-domain (residues 72-138), 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. Comparison of the structure of PhoIF-5A with those of archaeal homologues from Methanococcus jannaschii and Pyrobaculum aerophilum showed that the N-domains could be superimposed with root mean square deviation (rmsd) values of 0.679 and 0.624 A, while the C-domains gave higher values of 1.824 and 1.329 A, respectively. 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.
Yao
Min
M
Division of Biological Science, Graduate School of Science, Hokkaido University, Sapporo 066-0810.
Ohsawa
Akiko
A
Kikukawa
Shingo
S
Tanaka
Isao
I
Kimura
Makoto
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D000097574:Eukaryotic Translation Initiation Factor 5A
D008239:Lysine; D010448:Peptide Initiation Factors; D012313:RNA; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C115531:aIF-5A; C100028:hypusine