PMID- 15537658
OWN - NLM
STAT- MEDLINE
DCOM- 20050308
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 4
DP  - 2005 Jan 28
TI  - A major histocompatibility complex-peptide-restricted antibody and t cell 
      receptor molecules recognize their target by distinct binding modes: crystal 
      structure of human leukocyte antigen (HLA)-A1-MAGE-A1 in complex with FAB-HYB3.
PG  - 2972-80
AB  - Antibodies with T cell receptor-like specificity possess a considerable 
      diagnostic and therapeutic potential, but the structural basis of the interaction 
      between an antibody and an histocompatibility antigen has so far not been 
      determined. We present here the crystal structure (at 2.15 A resolution) of the 
      recombinant, affinity-matured human antibody fragment Fab-Hyb3 bound to the 
      tumor-associated human leukocyte antigen (HLA)/peptide complex HLA-A1.MAGE-A1. 
      Fab-Hyb3 employs a diagonal docking mode resembling that of T cell receptors. 
      However, other than these natural ligands, the antibody uses only four of its six 
      complementarity-determining regions for direct interactions with the target. It 
      recognizes the C-terminal half of the MAGE-A1 peptide, the HLA-A1 alpha1-helix, 
      and N-terminal residues of the alpha2-helix, accompanied by a large tilting angle 
      between the two types of molecules within the complex. Interestingly, only a 
      single hydrogen bond between a peptide side chain and Fab-Hyb3 contributes to the 
      interaction, but large buried surface areas with pronounced shape complementarity 
      assure high affinity and specificity for MAGE-A1. The HLA-A1.MAGE-A1.antibody 
      structure is discussed in comparison with those of natural ligands recognizing 
      HLA.peptide complexes.
FAU - Hulsmeyer, Martin
AU  - Hulsmeyer M
AD  - Institut fur Chemie/Kristallographie, Freie Universitat Berlin, 14195 Berlin, 
      Germany, Cellectis, 93235 Romainville, France.
FAU - Chames, Patrick
AU  - Chames P
FAU - Hillig, Roman C
AU  - Hillig RC
FAU - Stanfield, Robyn L
AU  - Stanfield RL
FAU - Held, Gerhard
AU  - Held G
FAU - Coulie, Pierre G
AU  - Coulie PG
FAU - Alings, Claudia
AU  - Alings C
FAU - Wille, Gabriele
AU  - Wille G
FAU - Saenger, Wolfram
AU  - Saenger W
FAU - Uchanska-Ziegler, Barbara
AU  - Uchanska-Ziegler B
FAU - Hoogenboom, Hennie R
AU  - Hoogenboom HR
FAU - Ziegler, Andreas
AU  - Ziegler A
LA  - eng
SI  - PDB/1W72
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041110
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Ligands)
RN  - 0 (Melanoma-Specific Antigens)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, Neoplasm
MH  - Crystallography, X-Ray
MH  - HLA-A1 Antigen/*chemistry
MH  - Humans
MH  - Hydrogen Bonding
MH  - Immunoglobulin Fab Fragments/*chemistry
MH  - Ligands
MH  - *Major Histocompatibility Complex
MH  - Melanoma-Specific Antigens
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/*chemistry
MH  - Peptides/*chemistry
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - Water/chemistry
EDAT- 2004/11/13 09:00
MHDA- 2005/03/09 09:00
CRDT- 2004/11/13 09:00
PHST- 2004/11/13 09:00 [pubmed]
PHST- 2005/03/09 09:00 [medline]
PHST- 2004/11/13 09:00 [entrez]
AID - S0021-9258(20)76350-7 [pii]
AID - 10.1074/jbc.M411323200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Jan 28;280(4):2972-80. doi: 10.1074/jbc.M411323200. Epub 2004 
      Nov 10.