title: Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with an antigenic nonapeptide.
abstract: The three-dimensional structure of the Fab fragment of a monoclonal antibody (LNKB-2) to human interleukin-2 (IL-2) complexed with a synthetic antigenic nonapeptide, Ac-Lys-Pro-Leu-Glu-Glu-Val-Leu-Asn-Leu-OMe, has been determined at 3.0 A resolution. In the structure, four out of the six hypervariable loops of the Fab (complementarity determining regions [CDRs] L1, H1, H2, and H3) are involved in peptide association through hydrogen bonding, salt bridge formation, and hydrophobic interactions. The Tyr residues in the Fab antigen binding site play a major role in antigen-antibody recognition. The structures of the complexed and uncomplexed Fab were compared. In the antigen binding site the CDR-L1 loop of the antibody shows the largest structural changes upon peptide binding. The peptide adopts a mostly alpha-helical conformation similar to that in the epitope fragment 64-72 of the IL-2 antigen. The side chains of residues Leu 66, Val 69, and Leu 70, which are shielded internally in the IL-2 structure, are involved in interactions with the Fab in the complex studied. This indicates that antibody-antigen complexation involves a significant rearrangement of the epitope-containing region of the IL-2 with retention of the alpha-helical character of the epitope fragment.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow, Russia.
authors.forename: P V
authors.initials: PV
authors.lastname: Afonin
authors.forename: A V
authors.initials: AV
authors.lastname: Fokin
authors.forename: I N
authors.initials: IN
authors.lastname: Tsygannik
authors.forename: I Y
authors.initials: IY
authors.lastname: Mikhailova
authors.forename: L V
authors.initials: LV
authors.lastname: Onoprienko
authors.forename: I I
authors.initials: II
authors.lastname: Mikhaleva
authors.forename: V T
authors.initials: VT
authors.lastname: Ivanov
authors.forename: T Y
authors.initials: TY
authors.lastname: Mareeva
authors.forename: V A
authors.initials: VA
authors.lastname: Nesmeyanov
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.forename: W A
authors.initials: WA
authors.lastname: Pangborn
authors.forename: W L
authors.initials: WL
authors.lastname: Duax
authors.forename: V Z
authors.initials: VZ
authors.lastname: Pletnev
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007376:Interleukin-2 / Q000737:chemistry / Q000276:immunology*; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D010455:Peptides