PMID- 19582797
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20131121
IS  - 1099-1352 (Electronic)
IS  - 0952-3499 (Linking)
VI  - 22
IP  - 6
DP  - 2009 Nov-Dec
TI  - Structural modeling and biochemical studies reveal insights into the molecular 
      basis of the recognition of beta-2-microglobulin by antibody BBM.1.
PG  - 465-73
LID - 10.1002/jmr.964 [doi]
AB  - Human beta-2-microglobulin (beta2m) is the light chain of human leucocyte 
      antigen-I (HLA-I). It can disassociate from HLA-I and accumulate to cause serious 
      dialysis-related amyloidosis (DRA) in long-term hemodialysis patients. Monoclonal 
      antibody (mAb) BBM.1 can recognize both free-form and HLA-I associated beta2m. It 
      can be used for specific elimination of beta2m from serum and can induce 
      apoptosis of several types of tumor cells, and thus has great therapeutic 
      potential. In this study, we constructed structural models of the BBM.1 Fv 
      (fragment of the variable domain) and the BBM.1 Fv-beta2m complex, followed by 
      biochemical evaluation. Analysis of the optimal complex model reveals that the 
      previously identified immunodominant residues Glu(44) and Arg(45) of beta2m have 
      direct interactions with BBM.1, while Asp(38) exerts its function mainly via 
      stabilization of Arg(45). In addition, Arg(81) of beta2m is a newly identified 
      immunodominant residue to have direct interaction with BBM.1. Further modeling 
      study shows no steric conflict between the antibody and the HLA-I heavy chain. 
      These results provide insights into the molecular basis of the recognition of 
      beta2m by BBM.1 and explain why BBM.1 can bind both free-form and HLA-1 
      associated beta2m. This information could be exploited in the engineering and 
      improvement of BBM.1 and the development of other beta2m-targeting mAbs for 
      therapeutic purposes.
FAU - Du, Jiamu
AU  - Du J
AD  - State Key Laboratory of Molecular Biology and Research Center for Structural 
      Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for 
      Biological Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
FAU - Yang, Hui
AU  - Yang H
FAU - Peng, Baozhen
AU  - Peng B
FAU - Ding, Jianping
AU  - Ding J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Recognit
JT  - Journal of molecular recognition : JMR
JID - 9004580
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HLA Antigens)
RN  - 0 (beta 2-Microglobulin)
RN  - 0RH81L854J (Glutamine)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Antibodies, Monoclonal/*chemistry
MH  - Arginine/chemistry
MH  - Circular Dichroism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glutamine/chemistry
MH  - HLA Antigens/*chemistry
MH  - Humans
MH  - Hydrogen Bonding
MH  - Molecular Conformation
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Structure, Secondary
MH  - Renal Dialysis
MH  - Surface Plasmon Resonance
MH  - beta 2-Microglobulin/*chemistry
EDAT- 2009/07/08 09:00
MHDA- 2010/02/02 06:00
CRDT- 2009/07/08 09:00
PHST- 2009/07/08 09:00 [entrez]
PHST- 2009/07/08 09:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
AID - 10.1002/jmr.964 [doi]
PST - ppublish
SO  - J Mol Recognit. 2009 Nov-Dec;22(6):465-73. doi: 10.1002/jmr.964.