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Volumn 305, Issue 5691, 2004, Pages 1770-1773

Crystal structure of a shark single-domain antibody V region in complex with lysozyme

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODIES; ANTIGENS; BINDING ENERGY; CRYSTAL STRUCTURE;

EID: 4544250973     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1101148     Document Type: Article
Times cited : (251)

References (43)
  • 23
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    • M. Dumoulin et al., Nature 424, 783 (2003).
    • (2003) Nature , vol.424 , pp. 783
    • Dumoulin, M.1
  • 24
    • 4544375291 scopus 로고    scopus 로고
    • note
    • HH domains can access recessed cavities, such as the HEL active-site cleft, by means of long CDR3 loops (72).
  • 27
    • 4544237156 scopus 로고    scopus 로고
    • note
    • Materials and methods are available as supporting material on Science Online.
  • 28
    • 4544347737 scopus 로고    scopus 로고
    • note
    • The IgNAR CDR3 is 20 residues in length, spanning N84 to N103 (Gly-Leu-Gly-Val-Ala-Gly-Gly-Tyr-Cys-Asp-Tyr-Ala-Leu-Cys-Ser-Ser-Arg-Tyr-Ala- Glu).
  • 29
    • 4544329031 scopus 로고    scopus 로고
    • note
    • H domains of around 0.7 to 1.0 Å for 45 core Cα atoms.
  • 31
    • 4544254145 scopus 로고    scopus 로고
    • note
    • The IgNAR CDR1 has root mean square deviations from the cAb-Lys3 and cAb-RN05 CDR1s of 1.2 and 1.5 Å, respectively, for 15 Cα atoms (IgNAR residues N22 to N36).
  • 32
    • 4544273494 scopus 로고    scopus 로고
    • note
    • HH cAb-Lys3 also binds an epitope encompassing the recessed HEL active site, similarly using its CDR3 for access (12). Several murine antibodies to lysozyme (HyHEL10, HyHEL8, HyHEL26, and HyHEL63) recognize a common epitope around the active site, but do not penetrate this site as deeply as do cAb-Lys3 and IgNAR.
  • 33
    • 4544332298 scopus 로고    scopus 로고
    • note
    • HH domains AMB7 and AMD10 use all three CDR loops, but CDR1 contributes only 5% of the total buried surface area on the antibody upon antigen binding.
  • 34
    • 4544312065 scopus 로고    scopus 로고
    • note
    • HH domains. A total of 122 van der Waals contacts (table S2), eight hydrogen bonds, and three charged interactions are made between HEL and the IgNAR (table S4). The majority of the buried surface on the IgNAR V domain is contributed by CDR3 residues N85 to N89, N91, N93, N95 to N96, and N98 to N103 (75%), with the remainder by CDR1 N26 to N33 (Fig. 4). The HEL-IgNAR V region interface has a good shape-complementarity index of 0.70 (0.72 and 0.70 for crystal form 2) (27), with waters filling several cavities in the interface (fig. S4). A total of 14 water molecules contact both the IgNAR V domain and HEL, with 7 of these (waters 2, 4, 7, 8, 60, 114, and 266) sequestered from contact with external solvent.
  • 35
    • 4544349767 scopus 로고    scopus 로고
    • note
    • Type I and type II sequences are 90% identical. IgNAR type II V domains have only four conserved cysteines, rather than the six or more found in type I, and tend toward smaller CDR3 lengths [9 to 18 amino acids (26)].
  • 36
    • 4544295381 scopus 로고    scopus 로고
    • note
    • 93 of conventional V domains.
  • 37
    • 4544384330 scopus 로고    scopus 로고
    • note
    • N64 are under strong positive selection.
  • 40
    • 4544236559 scopus 로고    scopus 로고
    • note
    • Unexpectedly, a set of receptors (variable lymphocyte receptors) that may modulate immune recognition in lamprey has recently been identified. These receptors are arranged from leucine-rich repeats and may constitute a component of a primitive immune system in lampreys (41).
  • 41
    • 3142616423 scopus 로고    scopus 로고
    • Z. Pancer et al., Nature 430, 174 (2004).
    • (2004) Nature , vol.430 , pp. 174
    • Pancer, Z.1
  • 43
    • 4544345280 scopus 로고    scopus 로고
    • note
    • We thank P. Horton for technical assistance. I. Holton, G. Meigs, the staff of Advanced Light Source Beamline 8.3.1 for support during data collection, and The National Aquarium in Baltimore for meticulous care of the sharks. Supported by NIH grants GM38273 (R.L.S. and I.A.W.) and RR06603 (H.D. and M.F.F.). This is manuscript no. 16602-MB from The Scripps Research Institute. The coordinates and structure factors have been deposited in the Protein Data Bank (PDB) with accession codes 1SQ2 (crystal form 1) and 1T6V (crystal form 2).


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.