Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1

被引：220

作者：

Matsumiya, Shigeki

Yamaguchi, Yoshiki

Saito, Jun-ichi

Nagano, Mayumi

Sasakawa, Hiroaki

Otaki, Shizuo

Satoh, Mitsuo

Shitara, Kenya

Kato, Koichi

机构：

[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan

[2] Kyowa Hakko Kogyo Co Ltd, Med Chem Res Labs, Pharmaceut Res Ctr, Nagaizumi, Shizuoka 4118731, Japan

[3] Natl Inst Nat Sci, Inst Mol Sci, Okazaki, Aichi 4448787, Japan

[4] Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Ctr, Dept Antibody REs, Machida, Tokyo 1948533, Japan

[5] Glyence Co Ltd, Nagoya Life Sci Incubator 406, Chikusa Ku, Nagoya, Aichi 4740858, Japan

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2007年 / 368卷 / 03期

基金：

日本科学技术振兴机构;

关键词：

immunoglobulin G1; fucose; antibody-dependent cellular cytotoxicity; X-ray crystal structure analysis; NMR spectroscopy;

D O I：

10.1016/j.jmb.2007.02.034

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：

Removal of the fucose residue from the oligosaccharides attached to Asn297 of human immunoglobulin G1 (IgG1) results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to Fc gamma receptor IIIa. To provide structural insight into the mechanisms of affinity enhancement, we determined the crystal structure of the nonfucosylated Fc fragment and compared it with that of fucosylated Fc. The overall conformations of the fucosylated and nonfucosylated Fc fragments were similar except for hydration mode around Tyr296. Stable-isotope-assisted NMR analyses confirmed the similarity of the overall structures between fucosylated and nonfucosylated Fc fragments in solution. These data suggest that the glycoform-dependent ADCC enhancement is attributed to a subtle conformational alteration in a limited region of IgG1-Fc. Furthermore, the electron density maps revealed that the traces between Asp280 and Asn297 of our fucosylated and. nonfucosylated Fc crystals were both different from that in previously reported isomorphous Fc crystals. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：767 / 779

页数：13

共 58 条

[1] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
BAILEY, S
[J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
[2] The Protein Data Bank
Berman, HM
Westbrook, J
Feng, Z
Gilliland, G
Bhat, TN
Weissig, H
Shindyalov, IN
Bourne, PE
[J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (01) : 235 - 242
[3] Recent changes to RasMol, recombining the variants
Bernstein, HJ
[J]. TRENDS IN BIOCHEMICAL SCIENCES, 2000, 25 (09) : 453 - 455
[4] HUMAN-ANTIBODY EFFECTOR FUNCTION
BURTON, DR
WOOF, JM
[J]. ADVANCES IN IMMUNOLOGY, 1992, 51 : 1 - +
[5] Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction
Corper, AL
Sohi, MK
Bonagura, VR
Steinitz, M
Jefferis, R
Feinstein, A
Beale, D
Taussig, MJ
Sutton, BJ
[J]. NATURE STRUCTURAL BIOLOGY, 1997, 4 (05) : 374 - 381
[6] Davies J, 2001, BIOTECHNOL BIOENG, V74, P288, DOI 10.1002/bit.1119
[7] CRYSTALLOGRAPHIC STRUCTURAL STUDIES OF A HUMAN FC FRAGMENT .2. COMPLETE MODEL BASED ON A FOURIER MAP AT 3.5 A RESOLUTION
DEISENHOFER, J
COLMAN, PM
EPP, O
HUBER, R
[J]. HOPPE-SEYLERS ZEITSCHRIFT FUR PHYSIOLOGISCHE CHEMIE, 1976, 357 (10): : 1421 - 1434
[8] CRYSTALLOGRAPHIC REFINEMENT AND ATOMIC MODELS OF A HUMAN FC FRAGMENT AND ITS COMPLEX WITH FRAGMENT-B OF PROTEIN-A FROM STAPHYLOCOCCUS-AUREUS AT 2.9-A AND 2.8-A RESOLUTION
DEISENHOFER, J
[J]. BIOCHEMISTRY, 1981, 20 (09) : 2361 - 2370
[9] Convergent solutions to binding at a protein-protein interface
DeLano, WL
Ultsch, MH
de Vos, AM
Wells, JA
[J]. SCIENCE, 2000, 287 (5456) : 1279 - 1283
[10] Edberg JC, 1997, J IMMUNOL, V159, P3849

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