title: Limited tryptic digestion of recombinant human interleukin-2: structure-binding relationships with the alpha chain of the interleukin-2 receptor.
abstract: The surface topography and structural features of interleukin-2 (IL-2) in relation to its interaction with the alpha subunit of its receptor (IL-2R alpha) have been probed by limited tryptic digestion followed by detailed structural analyses. Four sensitive cleavage sites in IL-2 (Lys8, Lys9, Lys35, and Arg38) were identified as surface amino acids, suggesting that they are potential binding sites for IL-2R alpha. To examine the involvement of these residues in IL-2R alpha binding, a truncated IL-2 molecule lacking the amino-terminal residues through Arg38 was generated and it was found to be incapable of binding IL-2R alpha in a solid-phase receptor binding sequencing assay. These studies have led to the conclusion that the IL-2R alpha contact region of IL-2 includes residues Lys35 and Arg38. This finding is supported by the refined three-dimensional structure of IL-2 in which these residues are located outside of the compact bundle of four helices and thus are readily available for interaction with IL-2R alpha.
authors.affiliation: Biotechnology Department, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110.
authors.forename: K
authors.initials: K
authors.lastname: Hollfelder
authors.forename: F
authors.initials: F
authors.lastname: Rabban
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: Y C
authors.initials: YC
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014357:Trypsin
chemical_list: D007376:Interleukin-2; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014357:Trypsin