• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jan 9, 1996; 93(1): 7–12.
PMCID: PMC40169

Interactions of protein antigens with antibodies.

Abstract

There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other protein-protein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogen-bond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding. For the most studied antigen, lysozyme, the epitopes for four antibodies occupy approximately 45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Davies DR, Padlan EA, Sheriff S. Antibody-antigen complexes. Annu Rev Biochem. 1990;59:439–473. [PubMed]
  • Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem. 1990 Sep 25;265(27):16027–16030. [PubMed]
  • Padlan EA. Anatomy of the antibody molecule. Mol Immunol. 1994 Feb;31(3):169–217. [PubMed]
  • Wilson IA, Stanfield RL. Antibody-antigen interactions: new structures and new conformational changes. Curr Opin Struct Biol. 1994 Dec;4(6):857–867. [PubMed]
  • Braden BC, Poljak RJ. Structural features of the reactions between antibodies and protein antigens. FASEB J. 1995 Jan;9(1):9–16. [PubMed]
  • Amit AG, Mariuzza RA, Phillips SE, Poljak RJ. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science. 1986 Aug 15;233(4765):747–753. [PubMed]
  • Fischmann TO, Bentley GA, Bhat TN, Boulot G, Mariuzza RA, Phillips SE, Tello D, Poljak RJ. Crystallographic refinement of the three-dimensional structure of the FabD1.3-lysozyme complex at 2.5-A resolution. J Biol Chem. 1991 Jul 15;266(20):12915–12920. [PubMed]
  • Bhat TN, Bentley GA, Fischmann TO, Boulot G, Poljak RJ. Small rearrangements in structures of Fv and Fab fragments of antibody D1.3 on antigen binding. Nature. 1990 Oct 4;347(6292):483–485. [PubMed]
  • Bhat TN, Bentley GA, Boulot G, Greene MI, Tello D, Dall'Acqua W, Souchon H, Schwarz FP, Mariuzza RA, Poljak RJ. Bound water molecules and conformational stabilization help mediate an antigen-antibody association. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1089–1093. [PMC free article] [PubMed]
  • Sheriff S, Silverton EW, Padlan EA, Cohen GH, Smith-Gill SJ, Finzel BC, Davies DR. Three-dimensional structure of an antibody-antigen complex. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8075–8079. [PMC free article] [PubMed]
  • Padlan EA, Silverton EW, Sheriff S, Cohen GH, Smith-Gill SJ, Davies DR. Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5938–5942. [PMC free article] [PubMed]
  • Chitarra V, Alzari PM, Bentley GA, Bhat TN, Eiselé JL, Houdusse A, Lescar J, Souchon H, Poljak RJ. Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7711–7715. [PMC free article] [PubMed]
  • Braden BC, Souchon H, Eiselé JL, Bentley GA, Bhat TN, Navaza J, Poljak RJ. Three-dimensional structures of the free and the antigen-complexed Fab from monoclonal anti-lysozyme antibody D44.1. J Mol Biol. 1994 Nov 4;243(4):767–781. [PubMed]
  • Bentley GA, Boulot G, Riottot MM, Poljak RJ. Three-dimensional structure of an idiotope-anti-idiotope complex. Nature. 1990 Nov 15;348(6298):254–257. [PubMed]
  • Benjamin DC, Williams DC, Jr, Smith-Gill SJ, Rule GS. Long-range changes in a protein antigen due to antigen-antibody interaction. Biochemistry. 1992 Oct 13;31(40):9539–9545. [PubMed]
  • Hibbits KA, Gill DS, Willson RC. Isothermal titration calorimetric study of the association of hen egg lysozyme and the anti-lysozyme antibody HyHEL-5. Biochemistry. 1994 Mar 29;33(12):3584–3590. [PubMed]
  • Tello D, Goldbaum FA, Mariuzza RA, Ysern X, Schwarz FP, Poljak RJ. Three-dimensional structure and thermodynamics of antigen binding by anti-lysozyme antibodies. Biochem Soc Trans. 1993 Nov;21(4):943–946. [PubMed]
  • Newman MA, Mainhart CR, Mallett CP, Lavoie TB, Smith-Gill SJ. Patterns of antibody specificity during the BALB/c immune response to hen eggwhite lysozyme. J Immunol. 1992 Nov 15;149(10):3260–3272. [PubMed]
  • Varghese JN, Laver WG, Colman PM. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature. 1983 May 5;303(5912):35–40. [PubMed]
  • Varghese JN, Colman PM. Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. J Mol Biol. 1991 Sep 20;221(2):473–486. [PubMed]
  • Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, Air GM, Webster RG. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature. 326(6111):358–363. [PubMed]
  • Tulip WR, Varghese JN, Webster RG, Air GM, Laver WG, Colman PM. Crystal structures of neuraminidase-antibody complexes. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):257–263. [PubMed]
  • Tulip WR, Varghese JN, Laver WG, Webster RG, Colman PM. Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. J Mol Biol. 1992 Sep 5;227(1):122–148. [PubMed]
  • Sheriff S, Hendrickson WA, Smith JL. Structure of myohemerythrin in the azidomet state at 1.7/1.3 A resolution. J Mol Biol. 1987 Sep 20;197(2):273–296. [PubMed]
  • Malby RL, Tulip WR, Harley VR, McKimm-Breschkin JL, Laver WG, Webster RG, Colman PM. The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody. Structure. 1994 Aug 15;2(8):733–746. [PubMed]
  • Colman PM. Influenza virus neuraminidase: structure, antibodies, and inhibitors. Protein Sci. 1994 Oct;3(10):1687–1696. [PMC free article] [PubMed]
  • Prasad L, Sharma S, Vandonselaar M, Quail JW, Lee JS, Waygood EB, Wilson KS, Dauter Z, Delbaere LT. Evaluation of mutagenesis for epitope mapping. Structure of an antibody-protein antigen complex. J Biol Chem. 1993 May 25;268(15):10705–10708. [PubMed]
  • Jerne NK. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed]
  • Gaulton GN, Greene MI. Idiotypic mimicry of biological receptors. Annu Rev Immunol. 1986;4:253–280. [PubMed]
  • Pan Y, Yuhasz SC, Amzel LM. Anti-idiotypic antibodies: biological function and structural studies. FASEB J. 1995 Jan;9(1):43–49. [PubMed]
  • Garcia KC, Ronco PM, Verroust PJ, Brünger AT, Amzel LM. Three-dimensional structure of an angiotensin II-Fab complex at 3 A: hormone recognition by an anti-idiotypic antibody. Science. 1992 Jul 24;257(5069):502–507. [PubMed]
  • Tello D, Eisenstein E, Schwarz FP, Goldbaum FA, Fields BA, Mariuzza RA, Poljak RJ. Structural and physicochemical analysis of the reaction between the anti-lysozyme antibody D1.3 and the anti-idiotopic antibodies E225 and E5.2. J Mol Recognit. 1994 Mar;7(1):57–62. [PubMed]
  • Ross PD, Subramanian S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry. 1981 May 26;20(11):3096–3102. [PubMed]
  • Ban N, Escobar C, Garcia R, Hasel K, Day J, Greenwood A, McPherson A. Crystal structure of an idiotype-anti-idiotype Fab complex. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1604–1608. [PMC free article] [PubMed]
  • Evans SV, Rose DR, To R, Young NM, Bundle DR. Exploring the mimicry of polysaccharide antigens by anti-idiotypic antibodies. The crystallization, molecular replacement, and refinement to 2.8 A resolution of an idiotope-anti-idiotope Fab complex and of the unliganded anti-idiotope Fab. J Mol Biol. 1994 Sep 2;241(5):691–705. [PubMed]
  • Kabat EA, Wu TT, Bilofsky H. Unusual distributions of amino acids in complementarity-determining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in specificity of antibody-combining sites. J Biol Chem. 1977 Oct 10;252(19):6609–6616. [PubMed]
  • Padlan EA. On the nature of antibody combining sites: unusual structural features that may confer on these sites an enhanced capacity for binding ligands. Proteins. 1990;7(2):112–124. [PubMed]
  • Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem. 1990 Sep 25;265(27):16027–16030. [PubMed]
  • Mian IS, Bradwell AR, Olson AJ. Structure, function and properties of antibody binding sites. J Mol Biol. 1991 Jan 5;217(1):133–151. [PubMed]
  • Lea S, Stuart D. Analysis of antigenic surfaces of proteins. FASEB J. 1995 Jan;9(1):87–93. [PubMed]
  • Smith-Gill SJ, Wilson AC, Potter M, Prager EM, Feldmann RJ, Mainhart CR. Mapping the antigenic epitope for a monoclonal antibody against lysozyme. J Immunol. 1982 Jan;128(1):314–322. [PubMed]
  • Cunningham BC, Wells JA. Comparison of a structural and a functional epitope. J Mol Biol. 1993 Dec 5;234(3):554–563. [PubMed]
  • Wells JA. Binding in the growth hormone receptor complex. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):1–6. [PMC free article] [PubMed]
  • Sharma S, Georges F, Delbaere LT, Lee JS, Klevit RE, Waygood EB. Epitope mapping by mutagenesis distinguishes between the two tertiary structures of the histidine-containing protein HPr. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4877–4881. [PMC free article] [PubMed]
  • Klevit RE, Waygood EB. Two-dimensional 1H NMR studies of histidine-containing protein from Escherichia coli. 3. Secondary and tertiary structure as determined by NMR. Biochemistry. 1986 Nov 18;25(23):7774–7781. [PubMed]
  • el-Kabbani OA, Waygood EB, Delbaere LT. Tertiary structure of histidine-containing protein of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli. J Biol Chem. 1987 Sep 25;262(27):12926–12929. [PubMed]
  • Paterson Y, Englander SW, Roder H. An antibody binding site on cytochrome c defined by hydrogen exchange and two-dimensional NMR. Science. 1990 Aug 17;249(4970):755–759. [PMC free article] [PubMed]
  • Mylvaganam SE, Paterson Y, Kaiser K, Bowdish K, Getzoff ED. Biochemical implications from the variable gene sequences of an anti-cytochrome c antibody and crystallographic characterization of its antigen-binding fragment in free and antigen-complexed forms. J Mol Biol. 1991 Sep 20;221(2):455–462. [PubMed]
  • Davies DR, Padlan EA. Twisting into shape. Curr Biol. 1992 May;2(5):254–256. [PubMed]
  • Stanfield RL, Takimoto-Kamimura M, Rini JM, Profy AT, Wilson IA. Major antigen-induced domain rearrangements in an antibody. Structure. 1993 Oct 15;1(2):83–93. [PubMed]
  • Kurinov IV, Harrison RW. The influence of temperature on lysozyme crystals. Structure and dynamics of protein and water. Acta Crystallogr D Biol Crystallogr. 1995 Jan 1;51(Pt 1):98–109. [PubMed]
  • Harata K. X-ray structure of a monoclinic form of hen egg-white lysozyme crystallized at 313 K. Comparison of two independent molecules. Acta Crystallogr D Biol Crystallogr. 1994 May 1;50(Pt 3):250–257. [PubMed]
  • Ramanadham M, Sieker LC, Jensen LH. Refinement of triclinic lysozyme: II. The method of stereochemically restrained least squares. Acta Crystallogr B. 1990 Feb 1;46(Pt 1):63–69. [PubMed]
  • Clackson T, Wells JA. A hot spot of binding energy in a hormone-receptor interface. Science. 1995 Jan 20;267(5196):383–386. [PubMed]
  • Chacko S, Silverton E, Kam-Morgan L, Smith-Gill S, Cohen G, Davies D. Structure of an antibody-lysozyme complex unexpected effect of conservative mutation. J Mol Biol. 1995 Jan 20;245(3):261–274. [PubMed]
  • Tulip WR, Varghese JN, Webster RG, Laver WG, Colman PM. Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface. J Mol Biol. 1992 Sep 5;227(1):149–159. [PubMed]
  • Ysern X, Fields BA, Bhat TN, Goldbaum FA, Dall'Acqua W, Schwarz FP, Poljak RJ, Mariuzza RA. Solvent rearrangement in an antigen-antibody interface introduced by site-directed mutagenesis of the antibody combining site. J Mol Biol. 1994 May 13;238(4):496–500. [PubMed]
  • Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):13–20. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links