Evidence from sequence information that the interleukin-1 receptor is a transmembrane GTPase.
Evidence is presented that the cytoplasmic domain of the type I interleukin-1 receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic amino acids that suggest a structural relatedness to the ras protooncogene protein and other members of the GTPase superfamily, despite a lack of significant detectable sequence homology. When the hydrophobic segments of the IL-1R were aligned with similar segments of the GTPases, it became apparent that the IL-1Rs possess a number of conserved amino acids that represent plausible functional residues for base-specific binding of GTP, magnesium chelation, and phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues were found that is identical between ras and the IL-1R, and which is positioned to form part of the guanine base binding pocket. If this model is correct, then the IL-1Rs possess a highly conserved effector protein binding region, but one that is entirely unrelated to the effector regions of other superfamily members. Therefore, if the IL-1R is indeed a GTPase, then its activation function may be directed to as-yet unrecognized effector target proteins, as part of a unique cellular signal transduction pathway.
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Protein Research Laboratories, Inc., San Diego, California 92126, USA.
D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D017124:Conserved Sequence; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006860:Hydrogen Bonding; D008274:Magnesium / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010710:Phosphates / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017472:Receptors, Interleukin-1 / Q000737:chemistry* / Q000378:metabolism; D017385:Sequence Homology; D015398:Signal Transduction
D010446:Peptide Fragments; D010710:Phosphates; D017472:Receptors, Interleukin-1; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D008274:Magnesium