scholarly journals The mycoplasma surface proteins MIB and MIP promote the dissociation of the antibody-antigen interaction

2021 ◽  
Vol 7 (10) ◽  
pp. eabf2403
Author(s):  
Pierre Nottelet ◽  
Laure Bataille ◽  
Geraldine Gourgues ◽  
Robin Anger ◽  
Carole Lartigue ◽  
...  
Keyword(s):  
Surface Proteins ◽  
Mycoplasma Species ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Fab Fragment ◽  
Cryo Electron Microscopy ◽  
Antigen Complex ◽  
Antigen Interaction ◽  
Immunoglobulin Binding

Mycoplasma immunoglobulin binding (MIB) and mycoplasma immunoglobulin protease (MIP) are surface proteins found in the majority of mycoplasma species, acting sequentially to capture antibodies and cleave off their VH domains. Cryo–electron microscopy structures show how MIB and MIP bind to a Fab fragment in a “hug of death” mechanism. As a result, the orientation of the VL and VH domains is twisted out of alignment, disrupting the antigen binding site. We also show that MIB-MIP has the ability to promote the dissociation of the antibody-antigen complex. This system is functional in cells and protects mycoplasmas from antibody-mediated agglutination. These results highlight the key role of the MIB-MIP system in immunity evasion by mycoplasmas through an unprecedented mechanism, and open exciting perspectives to use these proteins as potential tools in the antibody field.

Role of the mobility of antigen binding site in high affinity antibody elucidated by surface plasmon resonance

2016 ◽  
Vol 161 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Natsuki Fukuda ◽  
Yoshiaki Suwa ◽  
Makiyo Uchida ◽  
Yoshihiro Kobashigawa ◽  
Hideshi Yokoyama ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Binding Site ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
High Affinity

scholarly journals Antibody-induced uncoating of human rhinovirus B14

2017 ◽  
Vol 114 (30) ◽  
pp. 8017-8022 ◽  
Author(s):  
Yangchao Dong ◽  
Yue Liu ◽  
Wen Jiang ◽  
Thomas J. Smith ◽  
Zhikai Xu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Virus Infection ◽  
Conformational Changes ◽  
Neutralizing Antibody ◽  
Antigen Binding ◽  
Fab Fragment ◽  
Cryo Electron Microscopy ◽  
Virus Complex ◽  
Positive Strand Rna ◽  
Icosahedral Capsid

Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody–virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.

scholarly journals Structure of the Anti-C60 Fullerene Antibody Fab Fragment: Structural Determinants of Fullerene Binding

Acta Naturae ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 58-65 ◽  
Author(s):  
E. M. Osipov ◽  
O. D. Hendrickson ◽  
T. V. Tikhonova ◽  
A. V. Zherdev ◽  
O. N. Solopova ◽  
...  
Keyword(s):  
Binding Site ◽  
Hydrophobic Surface ◽  
Binding Pocket ◽  
C60 Fullerene ◽  
Antigen Binding ◽  
Structural Determinants ◽  
Antigen Binding Site ◽  
Fab Fragment ◽  
X Ray Crystallography ◽  
Solvent Accessible Area

The structure of the anti-C60 fullerene antibody Fab fragment (FabC60) was solved by X-ray crystallography. The computer-aided docking of C60 into the antigen-binding pocket of FabC60 showed that binding of C60 to FabC60 is governed by the enthalpy and entropy; namely, by - stacking interactions with aromatic residues of the antigen-binding site and reduction of the solvent-accessible area of the hydrophobic surface of C60. A fragment of the mobile CDR H3 loop located on the surface of FabC60 interferes with C60 binding in the antigen-binding site, thereby resulting in low antibody affinity for C60. The structure of apo-FabC60 has been deposited with pdbid 6H3H.

scholarly journals The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Fu-Lien Hsieh ◽  
Matthew K Higgins
Keyword(s):  
Immune Cell ◽  
Adaptive Immune System ◽  
Antigen Recognition ◽  
Binding Potential ◽  
Human Antibody ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Fab Fragment ◽  
Cell Recruitment ◽  
Critical Components

Antibodies are critical components of the human adaptive immune system, providing versatile scaffolds to display diverse antigen-binding surfaces. Nevertheless, most antibodies have similar architectures, with the variable immunoglobulin domains of the heavy and light chain each providing three hypervariable loops, which are varied to generate diversity. The recent identification of a novel class of antibody in humans from malaria endemic regions of Africa was therefore surprising as one hypervariable loop contains the entire collagen-binding domain of human LAIR1. Here, we present the structure of the Fab fragment of such an antibody. We show that its antigen-binding site has adopted an architecture that positions LAIR1, while itself being occluded. This therefore represents a novel means of antigen recognition, in which the Fab fragment of an antibody acts as an adaptor, linking a human protein insert with antigen-binding potential to the constant antibody regions which mediate immune cell recruitment.

scholarly journals Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody

2006 ◽  
Vol 395 (3) ◽  
pp. 473-481 ◽  
Author(s):  
Paul A. Ramsland ◽  
Simon S. Terzyan ◽  
Gwendolyn Cloud ◽  
Christina R. Bourne ◽  
William Farrugia ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Three Dimensional ◽  
Catalytic Triad ◽  
Dimensional Structure ◽  
Gel Point ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Fab Fragment ◽  
Peripheral Tissues ◽  
Fragment Antigen Binding

The 2.6 Å (1 Å=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenström's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611–39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024–14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds.

scholarly journals The Genomic Organisation of the TRA/TRD Locus Validates the Peculiar Characteristics of Dromedary δ-Chain Expression

2021 ◽  
Author(s):  
Serafina Massari ◽  
Giovanna Linguiti ◽  
Francesco Giannico ◽  
Pietro D'Addabbo ◽  
Salvatrice Maria Ciccarese ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Receptors ◽  
Somatic Hypermutation ◽  
Genomic Structure ◽  
Mammalian Species ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Germline Genes ◽  
Genomic Organisation

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

scholarly journals Contribution of HLA Class II Genes, DRB4*01:01, DRB1*07:01, and DQB1*03:03:2 to Clinical Features of Vitiligo Disease in Iranian Population

2021 ◽  
Author(s):  
Roya Ghaffarnia ◽  
Zahra Saffarian ◽  
Majid Shahbazi ◽  
Mahdi Zamani
Keyword(s):  
Late Onset ◽  
Class Ii ◽  
Hla Class Ii ◽  
Iranian Population ◽  
Antigen Binding ◽  
Specific Primer ◽  
Antigen Binding Site ◽  
Salting Out ◽  
Pcr Method

Abstract Background: Vitiligo is a multifactorial depigmentation condition, which is due to skin melanocyte destruction. The increased expression of HLA class II genes in patients with pre-lesions of Vitiligo suggests an important role for the participation of immune response in the Vitiligo development. Recent studies progressively focused on HLA-DRB1 and DQB1 genes. In this study, we have evaluated the association and role of HLA-DRB4*01:01, -DRB1*07:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population.Methods: First, Genomic DNA from peripheral blood of 125 unrelated Vitiligo patients and 100 unrelated healthy controls were extracted through salting-out method. Then, HLA CLASS II genotyping were performed using sequence-specific primer PCR method. Finally, the clinical relevance of the testing for these genotypes were evaluated by applying the PcPPV (prevalence-corrected positive predictive value) formula.Results: Our results indicated the positive associations of DRB4*01:01 and DRB1*07:01 allelic genes with early-onset Vitiligo (P= 0.024 and 0.022, respectively). The DRB4*01:01 also showed a strong protection against late-onset Vitiligo (P= 0.0016, RR=0.360). Moreover, our data revealed that the DRB1*07:01 increases the susceptibility to Sporadic Vitiligo (P=0.030, RR=1.702). Furthermore, our findings proposed that elevated vulnerability of Vitiligo patients due to DRB4*01:01 and DRB1*07:01 alleles may be is correlated with the presence of amino acid Arginine at position 71 at pocket 4 on the antigen-binding site of the HLA-DRB1 receptor.Conclusion: Our findings on different subtypes of Vitiligo suggest that, despite a more apparent autoimmune involvement, a non-autoimmune nature for the etiology of Vitiligo could also be considered.

scholarly journals Structure of the full-length human Pannexin1 channel and insights into its role in pyroptosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sensen Zhang ◽  
Baolei Yuan ◽  
Jordy Homing Lam ◽  
Jun Zhou ◽  
Xuan Zhou ◽  
...  
Keyword(s):  
Md Simulation ◽  
Potential Role ◽  
Md Simulations ◽  
Full Length ◽  
Inflammasome Activation ◽  
Simulation Studies ◽  
Cryo Electron Microscopy ◽  
Gating Mechanism ◽  
Atp Efflux

AbstractPannexin1 (PANX1) is a large-pore ATP efflux channel with a broad distribution, which allows the exchange of molecules and ions smaller than 1 kDa between the cytoplasm and extracellular space. In this study, we show that in human macrophages PANX1 expression is upregulated by diverse stimuli that promote pyroptosis, which is reminiscent of the previously reported lipopolysaccharide-induced upregulation of PANX1 during inflammasome activation. To further elucidate the function of PANX1, we propose the full-length human Pannexin1 (hPANX1) model through cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulation studies, establishing hPANX1 as a homo-heptamer and revealing that both the N-termini and C-termini protrude deeply into the channel pore funnel. MD simulations also elucidate key energetic features governing the channel that lay a foundation to understand the channel gating mechanism. Structural analyses, functional characterizations, and computational studies support the current hPANX1-MD model, suggesting the potential role of hPANX1 in pyroptosis during immune responses.

scholarly journals The Prognostic Role of LRIG Proteins in Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1361
Author(s):  
Zoia Razumova ◽  
Husam Oda ◽  
Igor Govorov ◽  
Eva Lundin ◽  
Ellinor Östensson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factor ◽  
Confidence Interval ◽  
Initial Study ◽  
Surface Proteins ◽  
University Hospital ◽  
Study Cohort ◽  
Risk Of Death

Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women’s and Children’s Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression-free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1-, LRIG2- and LRIG3-positive cells. A statistically significant association was observed between having a high number of LRIG3-positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958–0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09–0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated.

Sign in / Sign up

Export Citation Format

Share Document