scholarly journals Crystal Structure of Fcγ Receptor I and Its Implication in High Affinity γ-Immunoglobulin Binding

2011 ◽  
Vol 286 (47) ◽  
pp. 40608-40613 ◽  
Author(s):  
Jinghua Lu ◽  
Jeff L. Ellsworth ◽  
Nels Hamacher ◽  
Si Won Oak ◽  
Peter D. Sun
Keyword(s):  
Crystal Structure ◽  
Fcγ Receptor ◽  
High Affinity ◽  
Immunoglobulin Binding

scholarly journals Recognition of an α-helical hairpin in P22 large terminase by a synthetic antibody fragment

2020 ◽  
Vol 76 (9) ◽  
pp. 876-888
Author(s):  
Ravi K. Lokareddy ◽  
Ying-Hui Ko ◽  
Nathaniel Hong ◽  
Steven G. Doll ◽  
Marcin Paduch ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Recombinant Antibody ◽  
Antibody Fragment ◽  
Genome Packaging ◽  
Synthetic Antibody ◽  
High Affinity ◽  
N Terminus ◽  
Helical Hairpin ◽  
Accessible Surface

The genome-packaging motor of tailed bacteriophages and herpesviruses is a multisubunit protein complex formed by several copies of a large (TerL) and a small (TerS) terminase subunit. The motor assembles transiently at the portal protein vertex of an empty precursor capsid to power the energy-dependent packaging of viral DNA. Both the ATPase and nuclease activities associated with genome packaging reside in TerL. Structural studies of TerL from bacteriophage P22 have been hindered by the conformational flexibility of this enzyme and its susceptibility to proteolysis. Here, an unbiased, synthetic phage-display Fab library was screened and a panel of high-affinity Fabs against P22 TerL were identified. This led to the discovery of a recombinant antibody fragment, Fab4, that binds a 33-amino-acid α-helical hairpin at the N-terminus of TerL with an equilibrium dissociation constant K d of 71.5 nM. A 1.51 Å resolution crystal structure of Fab4 bound to the TerL epitope (TLE) together with a 1.15 Å resolution crystal structure of the unliganded Fab4, which is the highest resolution ever achieved for a Fab, elucidate the principles governing the recognition of this novel helical epitope. TLE adopts two different conformations in the asymmetric unit and buries as much as 1250 Å2 of solvent-accessible surface in Fab4. TLE recognition is primarily mediated by conformational changes in the third complementarity-determining region of the Fab4 heavy chain (CDR H3) that take place upon epitope binding. It is demonstrated that TLE can be introduced genetically at the N-terminus of a target protein, where it retains high-affinity binding to Fab4.

scholarly journals Inter-residue coupling contributes to high-affinity subtype-selective binding of α-bungarotoxin to nicotinic receptors

2013 ◽  
Vol 454 (2) ◽  
pp. 311-321 ◽  
Author(s):  
Steven M. Sine ◽  
Sun Huang ◽  
Shu-Xing Li ◽  
Corrie J. B. daCosta ◽  
Lin Chen
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Nicotinic Receptors ◽  
Radioligand Binding ◽  
Binding Domain ◽  
Tyrosine Residue ◽  
Selective Binding ◽  
Conserved Residues ◽  
High Affinity ◽  
Subtype Selective

On the basis of the crystal structure of a pentameric α7 ligand-binding domain chimaera with bound α-bungarotoxin, mutagenesis and radioligand-binding measurements show that high-affinity target-selective binding depends on interactions between a single conserved tyrosine residue in α7 and nearby conserved and non-conserved residues.

scholarly journals High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Robert Cheng ◽  
Brunella Felicetti ◽  
Shilpa Palan ◽  
Ian Toogood-Johnson ◽  
Christoph Scheich ◽  
...  
Keyword(s):  
Crystal Structure ◽  
High Resolution ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals Markedly Different Pathogenicity of Four Immunoglobulin G Isotype-Switch Variants of an Antierythrocyte Autoantibody Is Based on Their Capacity to Interact in Vivo with the Low-Affinity Fcγ Receptor III

2000 ◽  
Vol 191 (8) ◽  
pp. 1293-1302 ◽  
Author(s):  
Liliane Fossati-Jimack ◽  
Andreea Ioan-Facsinay ◽  
Luc Reininger ◽  
Yves Chicheportiche ◽  
Norihiko Watanabe ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Critical Role ◽  
Mouse Strains ◽  
Fcγ Receptor ◽  
High Affinity ◽  
Igg Isotypes ◽  
Ig G

Using three different Fcγ receptor (FcγR)-deficient mouse strains, we examined the induction of autoimmune hemolytic anemia by each of the four immunoglobulin (Ig)G isotype-switch variants of a 4C8 IgM antierythrocyte autoantibody and its relation to the contributions of the two FcγR, FcγRI, and FcγRIII, operative in the phagocytosis of opsonized particles. We found that the four IgG isotypes of this antibody displayed striking differences in pathogenicity, which were related to their respective capacity to interact in vivo with the two phagocytic FcγRs, defined as follows: IgG2a > IgG2b > IgG3/IgG1 for FcγRI, and IgG2a > IgG1 > IgG2b > IgG3 for FcγRIII. Accordingly, the IgG2a autoantibody exhibited the highest pathogenicity, ∼20–100-fold more potent than its IgG1 and IgG2b variants, respectively, while the IgG3 variant, which displays little interaction with these FcγRs, was not pathogenic at all. An unexpected critical role of the low-affinity FcγRIII was revealed by the use of two different IgG2a anti–red blood cell autoantibodies, which displayed a striking preferential utilization of FcγRIII, compared with the high-affinity FcγRI. This demonstration of the respective roles in vivo of four different IgG isotypes, and of two phagocytic FcγRs, in autoimmune hemolytic anemia highlights the major importance of the regulation of IgG isotype responses in autoantibody-mediated pathology and humoral immunity.

scholarly journals Crystal Structure of a Superantigen Bound to the High-Affinity, Zinc-Dependent Site on MHC Class II

Immunity ◽  
2001 ◽  
Vol 14 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Yili Li ◽  
Hongmin Li ◽  
Nazzareno Dimasi ◽  
John K. McCormick ◽  
Roland Martin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mhc Class Ii ◽  
Class Ii ◽  
High Affinity ◽  
Dependent Site

Crystal structure of a complex between interferon-γ and its soluble high-affinity receptor

Nature ◽  
1995 ◽  
Vol 376 (6537) ◽  
pp. 230-235 ◽  
Author(s):  
Mark R. Walter ◽  
William T. Windsor ◽  
Tattanahalli L. Nagabhushan ◽  
Daniel J. Lundell ◽  
Charles A. Lunn ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Interferon Γ ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor

scholarly journals Functional and Selective Targeting of Adenovirus to High-Affinity Fcγ Receptor I-Positive Cells by Using a Bispecific Hybrid Adapter

2001 ◽  
Vol 75 (1) ◽  
pp. 480-489 ◽  
Author(s):  
Christina Ebbinghaus ◽  
Ahmed Al-Jaibaji ◽  
Elisabeth Operschall ◽  
Angelika Schöffel ◽  
Isabelle Peter ◽  
...  
Keyword(s):  
Fold Increase ◽  
Adapter Protein ◽  
Fcγ Receptor ◽  
Monocytic Cell ◽  
Coxsackie Adenovirus Receptor ◽  
Amino Terminal ◽  
High Affinity ◽  
Selective Targeting ◽  
Human Monocytic Cell ◽  
Adenovirus Receptor

ABSTRACT Adenovirus (Ad) efficiently delivers its DNA genome into a variety of cells and tissues, provided that these cells express appropriate receptors, including the coxsackie-adenovirus receptor (CAR), which binds to the terminal knob domain of the viral capsid protein fiber. To render CAR-negative cells susceptible to Ad infection, we have produced a bispecific hybrid adapter protein consisting of the amino-terminal extracellular domain of the human CAR protein (CARex) and the Fc region of the human immunoglobulin G1 protein, comprising the hinge and the CH2 and CH3 regions. CARex-Fc was purified from COS7 cell supernatants and mixed with Ad particles, thus blocking Ad infection of CAR-positive but Fc receptor-negative cells. The functionality of the CARex domain was further confirmed by successful immunization of mice with CARex-Fc followed by selection of a monoclonal anti-human CAR antibody (E1-1), which blocked Ad infection of CAR-positive cells. When mixed with Ad expressing eGFP, CARex-Fc mediated an up to 250-fold increase of transgene expression in CAR-negative human monocytic cell lines expressing the high-affinity Fcγ receptor I (CD64) but not in cells expressing the low-affinity Fcγ receptor II (CD32) or III (CD16). These results open new perspectives for Ad-mediated cancer cell vaccination, including the treatment of acute myeloid leukemia.

scholarly journals Crystal Structure of a Mucus-binding Protein Repeat Reveals an Unexpected Functional Immunoglobulin Binding Activity

2009 ◽  
Vol 284 (47) ◽  
pp. 32444-32453 ◽  
Author(s):  
Donald A. MacKenzie ◽  
Louise E. Tailford ◽  
Andrew M. Hemmings ◽  
Nathalie Juge
Keyword(s):  
Crystal Structure ◽  
Binding Protein ◽  
Binding Activity ◽  
Immunoglobulin Binding
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