Flexibility and molecular recognition in the immune system.
Photon echo spectroscopy has been used to measure the response of three antibody-binding sites to perturbation from electronic excitation of a bound antigen, fluorescein. The three antibodies show motions that range in time scale from tens of femtoseconds to nanoseconds. Relative to the others, one antibody, 4-4-20, possesses a rigid binding site that likely results from a short and inflexible heavy chain complementarity-determining region 3 (HCDR3) loop and a critical Tyr that acts as a "molecular splint," rigidifying the antigen across its most flexible internal degree of freedom. The remaining two antibodies, 34F10 and 40G4, despite being generated against the same antigen, possess binding sites that are considerably more flexible. The more flexible combining sites likely result from longer HCDR3 loops and a deletion in the light chain complementarity-determining region 1 (LCDR1) that removes the critical Tyr residue. The binding site flexibilities may result in varying mechanisms of antigen recognition including lock-and-key, induced-fit, and conformational selection.
Jimenez
Ralph
R
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Drop CVN22, La Jolla, CA 92037, USA.
Salazar
Georgina
G
Baldridge
Kim K
KK
Romesberg
Floyd E
FE
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000941:Antigens / Q000737:chemistry*; D001666:Binding Sites, Antibody; D003198:Computer Simulation; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D000941:Antigens; D007143:Immunoglobulin Heavy Chains