STRUCTURE, FUNCTION AND PROPERTIES OF ANTIBODY-BINDING SITES

被引:410
作者
MIAN, IS
BRADWELL, AR
OLSON, AJ
机构
[1] Scripps Res Inst, RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
[2] UNIV BIRMINGHAM, SCH MED, DEPT IMMUNOL, BIRMINGHAM B15 2TJ, W MIDLANDS, ENGLAND
关键词
D O I
10.1016/0022-2836(91)90617-F
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Do antibody combining sites possess general properties that enable them to bind different antigens with varying affinities and to bind novel antigens? Here, we address this question by examining the physical and chemical characteristics most favourable for residues involved in antigen accommodation and binding. Amphipathic amino acids could readily tolerate the change of environment from hydrophilic to hydrophobic that occurs upon antibody-antigen complex formation. Residues that are large and can participate in a wide variety of van der Waals' and electrostatic interactions would permit binding to a range of antigens. Amino acids with flexible side-chains could generate a structurally plastic region, i.e. a binding site possessing the ability to mould itself around the antigen to improve complementarity of the interacting surfaces. Hence, antibodies could bind to an array of novel antigens using a limited set of residues interspersed with more unique residues to which greater binding specificity can be attributed. An individual antibody molecule could thus be cross-reactive and have the capacity to bind structurally similar ligands. The accommodation of variations in antigenic structure by modest combining site flexibility could make an important contribution to immune defence by allowing antibody binding to distinct but closely related pathogens. Tyr and Trp most readily fulfil these catholic physicochemical requirements and thus would be expected to be common in combining sites on theoretical grounds. Experimental support for this comes from three sources, (1) the high frequency of participation by these amino acids in the antigen binding observed in six crystallographically determined antibody-antigen complexes, (2) their frequent occurrence in the putative binding regions of antibodies as determined from structural and sequence data and (3) the potential for movement of their side-chains in known antibody binding sites and model systems. The six bound antigens comprise two small different haptens, non-overlapping regions of the same large protein and a 19 amino acid residue peptide. Out of a total of 85 complementarity determining region positions, only 37 locations (plus 3 framework) are directly involved in antigen interaction. Of these, light chain residue 91 is utilized by all the complexes examined, whilst light chain 32, light chain 96 and heavy chain 33 are employed by five out of the six. The binding sites in known antibody-antigen complexes as well as the postulated combining sites in free Fab fragments show similar characteristics with regard to the types of amino acids present. The possible role of other amino acids is also assessed. Potential implications for the combining regions of class I major histocompatibility molecules and the rational design of molecules are discussed. © 1991.
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页码:133 / 151
页数:19
相关论文
共 62 条
  • [1] ALZARI PM, 1988, ANNU REV IMMUNOL, V6, P555
  • [2] 3-DIMENSIONAL STRUCTURE OF AN ANTIGEN-ANTIBODY COMPLEX AT 2.8-A RESOLUTION
    AMIT, AG
    MARIUZZA, RA
    PHILLIPS, SEV
    POLJAK, RJ
    [J]. SCIENCE, 1986, 233 (4765) : 747 - 753
  • [3] ANTIBODIES AGAINST A PEPTIDE OF CHOLERA-TOXIN DIFFERING IN CROSS-REACTIVITY WITH THE TOXIN DIFFER IN THEIR SPECIFIC INTERACTIONS WITH THE PEPTIDE AS OBSERVED BY H-1-NMR SPECTROSCOPY
    ANGLISTER, J
    ZILBER, B
    [J]. BIOCHEMISTRY, 1990, 29 (04) : 921 - 928
  • [4] HYDROGEN-BONDING IN GLOBULAR-PROTEINS
    BAKER, EN
    HUBBARD, RE
    [J]. PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1984, 44 (02) : 97 - 179
  • [5] BEDZYK WD, 1990, J BIOL CHEM, V265, P133
  • [6] MOLECULAR EVENTS DURING MATURATION OF THE IMMUNE-RESPONSE TO OXAZOLONE
    BEREK, C
    GRIFFITHS, GM
    MILSTEIN, C
    [J]. NATURE, 1985, 316 (6027) : 412 - 418
  • [7] MUTATION DRIFT AND REPERTOIRE SHIFT IN THE MATURATION OF THE IMMUNE-RESPONSE
    BEREK, C
    MILSTEIN, C
    [J]. IMMUNOLOGICAL REVIEWS, 1987, 96 : 23 - 41
  • [8] PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
    BERNSTEIN, FC
    KOETZLE, TF
    WILLIAMS, GJB
    MEYER, EF
    BRICE, MD
    RODGERS, JR
    KENNARD, O
    SHIMANOUCHI, T
    TASUMI, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1977, 112 (03) : 535 - 542
  • [9] THE FOREIGN ANTIGEN-BINDING SITE AND T-CELL RECOGNITION REGIONS OF CLASS-I HISTOCOMPATIBILITY ANTIGENS
    BJORKMAN, PJ
    SAPER, MA
    SAMRAOUI, B
    BENNETT, WS
    STROMINGER, JL
    WILEY, DC
    [J]. NATURE, 1987, 329 (6139) : 512 - 518
  • [10] STRUCTURAL PLASTICITY BROADENS THE SPECIFICITY OF AN ENGINEERED PROTEASE
    BONE, R
    SILEN, JL
    AGARD, DA
    [J]. NATURE, 1989, 339 (6221) : 191 - 195