PMID- 7578050
OWN - NLM
STAT- MEDLINE
DCOM- 19951218
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 34
IP  - 44
DP  - 1995 Nov 7
TI  - Bent domain structure of recombinant human IgE-Fc in solution by X-ray and 
      neutron scattering in conjunction with an automated curve fitting procedure.
PG  - 14449-61
AB  - Human immunoglobulin E (IgE) consists of 14 domains, each with the characteristic 
      immunoglobulin fold structure. Compared with the 12-domain structure of 
      immunoglobulin G (IgG), IgE has an additional pair of domains (C epsilon 2) in 
      the Fc region in place of the hinge of IgG. The crystal structure of the 4-domain 
      Fc fragment of IgG is known, but not that of the 6-domain Fc fragment of IgE 
      (IgE-Fc). In order to elucidate the position of the C epsilon 2 domains in the 
      domain structure of IgE-Fc, IgE-Fc was studied by synchrotron X-ray and pulsed 
      neutron scattering. The upper limit on the X-ray radius of gyration RG which 
      determines macromolecular elongation was determined to be 3.52 +/- 0.14 nm. That 
      for the neutron RG (measured in 100% 2H2O buffers) was 3.53 +/- 0.05 nm. The 
      X-ray and neutron cross-sectional radii of gyration were 1.89 +/- 0.05 and 1.56 
      +/- 0.09 nm, respectively. The scattering curves were modeled on the basis of a 
      previously-predicted model for IgE-Fc (Helm, B. A., Ling, Y., Teale, C., Padlan, 
      E. A., & Bruggemann, M. (1991) Eur. J. Immunol. 21, 1543-1548). The extended 
      arrangement of domains in that model resulted in poor agreement with experimental 
      data. Interactive and automated procedures for the fitting of 
      crystallographically-derived domain models to scattering data were developed. 
      Each pair of C epsilon 2, C epsilon 3, and C epsilon 4 domains was translated and 
      rotated relative to the remaining structure in a comprehensive five-parameter 
      search of more than 37,000 models. Substantially improved agreement between the 
      experimental and calculated scattering curves was obtained. Bent models for 
      IgE-Fc in which the C epsilon 2 domain pair is rotated by at least 40-50 degrees 
      from its position in the previously predicted linear IgE model consistently gave 
      the best agreement with the X-ray and neutron scattering curves. Such a structure 
      for the Fc fragment accounts in part for the bent structure previously proposed 
      for intact human IgE, which is important for understanding the interaction 
      between IgE and its receptors.
FAU - Beavil, A J
AU  - Beavil AJ
AD  - Randall Institute, King's College London, U.K.
FAU - Young, R J
AU  - Young RJ
FAU - Sutton, B J
AU  - Sutton BJ
FAU - Perkins, S J
AU  - Perkins SJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Recombinant Proteins)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Computer Simulation
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Immunoglobulin E/*chemistry
MH  - Immunoglobulin Fc Fragments/*chemistry
MH  - Models, Molecular
MH  - Neutrons
MH  - Protein Folding
MH  - Recombinant Proteins/chemistry
EDAT- 1995/11/07 00:00
MHDA- 1995/11/07 00:01
CRDT- 1995/11/07 00:00
PHST- 1995/11/07 00:00 [pubmed]
PHST- 1995/11/07 00:01 [medline]
PHST- 1995/11/07 00:00 [entrez]
AID - 10.1021/bi00044a023 [doi]
PST - ppublish
SO  - Biochemistry. 1995 Nov 7;34(44):14449-61. doi: 10.1021/bi00044a023.