Phylogenetic analysis of eIF4E-family members.
BACKGROUND
Translation initiation in eukaryotes involves the recruitment of mRNA to the ribosome which is controlled by the translation factor eIF4E. eIF4E binds to the 5'-m7Gppp cap-structure of mRNA. Three dimensional structures of eIF4Es bound to cap-analogues resemble 'cupped-hands' in which the cap-structure is sandwiched between two conserved Trp residues (Trp-56 and Trp-102 of H. sapiens eIF4E). A third conserved Trp residue (Trp-166 of H. sapiens eIF4E) recognizes the 7-methyl moiety of the cap-structure. Assessment of GenBank NR and dbEST databases reveals that many organisms encode a number of proteins with homology to eIF4E. Little is understood about the relationships of these structurally related proteins to each other.


RESULTS
By combining sequence data deposited in the Genbank databases, we have identified sequences encoding 411 eIF4E-family members from 230 species. These sequences have been deposited into an internet-accessible database designed for sequence comparisons of eIF4E-family members. Most members can be grouped into one of three classes. Class I members carry Trp residues equivalent to Trp-43 and Trp-56 of H. sapiens eIF4E and appear to be present in all eukaryotes. Class II members, possess Trp-->Tyr/Phe/Leu and Trp-->Tyr/Phe substitutions relative to Trp-43 and Trp-56 of H. sapiens eIF4E, and can be identified in Metazoa, Viridiplantae, and Fungi. Class III members possess a Trp residue equivalent to Trp-43 of H. sapiens eIF4E but carry a Trp-->Cys/Tyr substitution relative to Trp-56 of H. sapiens eIF4E, and can be identified in Coelomata and Cnidaria. Some eIF4E-family members from Protista show extension or compaction relative to prototypical eIF4E-family members.


CONCLUSIONS
The expansion of sequenced cDNAs and genomic DNAs from all eukaryotic kingdoms has revealed a variety of proteins related in structure to eIF4E. Evolutionarily it seems that a single early eIF4E gene has undergone multiple gene duplications generating multiple structural classes, such that it is no longer possible to predict function from the primary amino acid sequence of an eIF4E-family member. The variety of eIF4E-family members provides a source of alternatives on the eIF4E structural theme that will benefit structure/function analyses and therapeutic drug design.
Joshi
Bhavesh
B
Center of Marine Biotechnology, Baltimore, MD 21202, USA. joshi@umbi.umd.edu
Lee
Kibwe
K
Maeder
Dennis L
DL
Jagus
Rosemary
R
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015195:Drug Design; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics*; D019143:Evolution, Molecular; D005802:Genes, MHC Class II; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012315:RNA Caps; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry
D018076:DNA, Complementary; D039561:Eukaryotic Initiation Factor-4E; D012315:RNA Caps; D014364:Tryptophan; D004247:DNA; D007930:Leucine; D003545:Cysteine