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Affinity maturation

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https://www.readbyqxmd.com/read/29782836/dancing-with-the-diva-hsp90-client-interactions
#1
REVIEW
Martina Radli, Stefan G D Rüdiger
The molecular chaperone Hsp90 is involved in the folding, maturation and degradation of a large number structurally and sequentially unrelated clients, often connected to serious diseases. Elucidating the principles of how Hsp90 recognises this large variety of substrates is essential for comprehending the mechanism of this chaperone machinery, as well as it is a prerequisite for the design of client specific drugs targeting Hsp90. Here, we discuss the recent progress in understanding the substrate recognition principles of Hsp90 and its implications for the role of Hsp90 in the lifecycle of (signalling) molecules...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29779865/gmf-as-an-actin-network-remodeling-factor
#2
REVIEW
Bruce L Goode, Meredith O Sweeney, Julian A Eskin
Glia maturation factor (GMF) has recently been established as a regulator of the actin cytoskeleton with a unique role in remodeling actin network architecture. Conserved from yeast to mammals, GMF is one of five members of the ADF-H family of actin regulatory proteins, which includes ADF/cofilin, Abp1/Drebrin, Twinfilin, and Coactosin. GMF does not bind actin, but instead binds the Arp2/3 complex with high affinity. Through this association, GMF catalyzes the debranching of actin filament networks and inhibits actin nucleation by Arp2/3 complex...
May 18, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29778602/structure-guided-combinatorial-engineering-facilitates-affinity-and-specificity-optimization-of-anti-cd81-antibodies
#3
Bryce Nelson, Jarrett Adams, Andreas Kuglstatter, Zhijian Li, Seth F Harris, Yang Liu, Sandya Bohini, Han Ma, Klaus Klumpp, Junjun Gao, Sachdev S Sidhu
Hepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block Hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop (LEL) in order to guide affinity maturation of two distinct antibodies by phage display...
May 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29775847/strategies-for-a-multi-stage-neutralizing-antibody-based-hiv-vaccine
#4
REVIEW
Raiees Andrabi, Jinal N Bhiman, Dennis R Burton
A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual features and are generated in a fraction of HIV-infected individuals through complex pathways. Current vaccine design approaches seek to trigger rare B cell precursors and then steer affinity maturation toward bnAbs in a multi-stage multi-component immunization approach. These vaccine design strategies have been facilitated by molecular descriptions of bnAb interactions with stabilized HIV trimers, the use of an array of sophisticated approaches for immunogen design, the development of novel animal models for immunogen evaluation and advanced technologies to interrogate antibody responses...
May 15, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#5
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29760533/cross-specificity-of-protective-human-antibodies-against-klebsiella-pneumoniae-lps-o-antigen
#6
Tim Rollenske, Valeria Szijarto, Jolanta Lukasiewicz, Luis M Guachalla, Katarina Stojkovic, Katharina Hartl, Lukas Stulik, Simone Kocher, Felix Lasitschka, Mohammed Al-Saeedi, Jutta Schröder-Braunstein, Moritz von Frankenberg, Gereon Gaebelein, Peter Hoffmann, Sabrina Klein, Klaus Heeg, Eszter Nagy, Gabor Nagy, Hedda Wardemann
Humoral immune responses to microbial polysaccharide surface antigens can prevent bacterial infection but are typically strain specific and fail to mediate broad protection against different serotypes. Here we describe a panel of affinity-matured monoclonal human antibodies from peripheral blood immunoglobulin M-positive (IgM+ ) and IgA+ memory B cells and clonally related intestinal plasmablasts, directed against the lipopolysaccharide (LPS) O-antigen of Klebsiella pneumoniae, an opportunistic pathogen and major cause of antibiotic-resistant nosocomial infections...
May 14, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29749564/affinity-maturation-of-an-antibody-for-the-uv-induced-dna-lesions-6-4-pyrimidine-pyrimidones
#7
Bingjie Kong, Yang Cao, Danni Wu, Lili An, Fanlei Ran, Yan Lin, Chen Ye, Hailin Wang, Haiying Hang
DNA lesions, associated mostly with minor changes in DNA structure, may induce permanent change in heritable coding information. Biochemically, these minor structural changes are difficult to be explored for generating high-affinity antibodies to detect specific DNA lesions in varying sequence contexts. Herein, we established a platform of bacterial display to facilitate antibodies to be matured with high affinity and high specificity against DNA lesions. To achieve this goal, we, for the first time, developed a two-round mutation/screening strategy: (1) using multiple lesion-containing DNA probes for primary maturation and (2) using single lesion-containing DNA probes for second maturation...
May 10, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29747159/seminal-plasma-influences-the-fertilizing-potential-of-cryopreserved-stallion-sperm
#8
Essraa M Al-Essawe, Margareta Wallgren, Manuela Wulf, Christine Aurich, Beatriz Macías-García, Ylva Sjunnesson, Jane M Morrell
Seminal plasma (SP) contains proteins that may influence cryosurvival and prevent capacitation-like changes due to freezing and thawing. The objective of this study was to investigate the effect of adding pooled SP from "good" (GF) or "bad" (BF) freezer stallions on sperm cells' fertilizing ability. "Good freezers" refers to stallions that usually produce ejaculates which can withstand cryopreservation, whilst "bad freezer" stallions produce ejaculates which cannot tolerate the freezing process...
April 26, 2018: Theriogenology
https://www.readbyqxmd.com/read/29744038/generating-and-repairing-genetically-programmed-dna-breaks-during-immunoglobulin-class-switch-recombination
#9
REVIEW
Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri, Bao Vuong
Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR...
2018: F1000Research
https://www.readbyqxmd.com/read/29739909/a-high-frequency-of-hiv-specific-circulating-follicular-helper-t-cells-is-associated-with-preserved-memory-b-cell-responses-in-hiv-controllers
#10
M Claireaux, M Galperin, D Benati, A Nouël, M Mukhopadhyay, J Klingler, P de Truchis, D Zucman, S Hendou, F Boufassa, C Moog, O Lambotte, L A Chakrabarti
Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+ T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet+ ), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA- CXCR5+ CD4+ T cell population, proved more frequent in the controller group ( P = 0...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29739835/nucleoside-modified-mrna-vaccines-induce-potent-t-follicular-helper-and-germinal-center-b-cell-responses
#11
Norbert Pardi, Michael J Hogan, Martin S Naradikian, Kaela Parkhouse, Derek W Cain, Letitia Jones, M Anthony Moody, Hans P Verkerke, Arpita Myles, Elinor Willis, Celia C LaBranche, David C Montefiori, Jenna L Lobby, Kevin O Saunders, Hua-Xin Liao, Bette T Korber, Laura L Sutherland, Richard M Scearce, Peter T Hraber, István Tombácz, Hiromi Muramatsu, Houping Ni, Daniel A Balikov, Charles Li, Barbara L Mui, Ying K Tam, Florian Krammer, Katalin Karikó, Patricia Polacino, Laurence C Eisenlohr, Thomas D Madden, Michael J Hope, Mark G Lewis, Kelly K Lee, Shiu-Lok Hu, Scott E Hensley, Michael P Cancro, Barton F Haynes, Drew Weissman
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates...
May 8, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29733317/split-bioid-proteomic-analysis-of-context-specific-protein-complexes-in-their-native-cellular-environment
#12
Isabel M Schopp, Julien Béthune
To complement existing affinity purification (AP) approaches for the identification of protein-protein interactions (PPI), enzymes have been introduced that allow the proximity-dependent labeling of proteins in living cells. One such enzyme, BirA* (used in the BioID approach), mediates the biotinylation of proteins within a range of approximately 10 nm. Hence, when fused to a protein of interest and expressed in cells, it allows the labeling of proximal proteins in their native environment. As opposed to AP that relies on the purification of assembled protein complexes, BioID detects proteins that have been marked within cells no matter whether they are still interacting with the protein of interest when they are isolated...
April 20, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29733023/identification-and-bioactivity-analysis-of-a-newly-identified-defensin-from-the-oyster-magallana-gigas
#13
Yubo Zhang, Pengfei Cui, Yashuo Wang, Shicui Zhang
The relatively conserved sequences of signal peptides and proregions that antimicrobial peptides (AMPs) contain have been successfully used to search for and identify novel AMPs from databases within the same lineages of fish and amphibians and across different animal classes. If such an approach is applicable to invertebrate species such as oyster has not yet been tested so far. In this study, we found a cDNA from the digestive gland of the oyster Magallana gigas, designated Mgdefdg, which contains two exons interspaced by one intron...
August 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29716522/the-cytidine-deaminase-under-representation-reporter-cdur-as-a-tool-to-study-evolution-of-sequences-under-deaminase-mutational-pressure
#14
Maxwell Shapiro, Stephen Meier, Thomas MacCarthy
BACKGROUND: Activation induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) are deaminases that mutate C to U on single-stranded DNA (ssDNA). AID is expressed primarily in germinal center B-cells, where it facilitates affinity maturation and class-switch recombination. APOBEC3 are a family of anti-viral proteins that act as part of the intrinsic immune response. In both cases, there are particular sequence motifs, also known as "mutation motifs", to which these deaminases prefer to bind and mutate...
May 2, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29709214/variant-proteins-stimulate-more-igm-gc-b-cells-revealing-a-mechanism-of-cross-reactive-recognition-by-antibody-memory
#15
Bronwen R Burton, Richard K Tennant, John Love, Richard W Titball, David C Wraith, Harry N White
Vaccines induce memory B-cells that provide high affinity secondary antibody responses to identical antigens. Memory B-cells can also re-instigate affinity maturation, but how this happens against antigenic variants is poorly understood despite its potential impact on driving broadly protective immunity against pathogens such as Influenza and Dengue. We immunised mice sequentially with identical or variant Dengue-virus envelope proteins and analysed antibody and germinal-centre (GC) responses. Variant protein boosts induced GC with higher proportions of IgM+ B-cells...
May 1, 2018: ELife
https://www.readbyqxmd.com/read/29709039/varicella-zoster-virus-productively-infects-human-natural-killer-cells-and-manipulates-phenotype
#16
Tessa Mollie Campbell, Brian Patrick McSharry, Megan Steain, Thomas Myles Ashhurst, Barry Slobedman, Allison Abendroth
Varicella zoster virus (VZV) is a ubiquitous human alphaherpesvirus, responsible for varicella upon primary infection and herpes zoster following reactivation from latency. To establish lifelong infection, VZV employs strategies to evade and manipulate the immune system to its advantage in disseminating virus. As innate lymphocytes, natural killer (NK) cells are part of the early immune response to infection, and have been implicated in controlling VZV infection in patients. Understanding of how VZV directly interacts with NK cells, however, has not been investigated in detail...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29708738/the-helicobacter-pylori-hypa%C3%A2-uree2-complex-contains-a-novel-high-affinity-ni-ii-binding-site
#17
Heidi Q Hu, Hsin-Ting Huang, Michael Maroney
Helicobacter pylori is a human pathogen that colonizes the stomach, is the major cause of ulcers, and has been associated with stomach cancers. In order to survive in the acidic environment of the stomach, H. pylori uses urease, a nickel-dependent enzyme, to produce ammonia for maintenance of cellular pH. The bacteria produce apo-urease in large quantities and activate it by incorporating nickel under acid shock conditions. Urease nickel incorporation requires the urease-specific metallochaperone UreE and the (UreFGH)2 maturation complex...
April 30, 2018: Biochemistry
https://www.readbyqxmd.com/read/29708552/rna-pull-down-procedure-to-identify-rna-targets-of-a-long-non-coding-rna
#18
Manon Torres, Denis Becquet, Séverine Guillen, Bénédicte Boyer, Mathias Moreno, Marie-Pierre Blanchard, Jean-Louis Franc, Anne-Marie François-Bellan
Long non-coding RNA (lncRNA), which are sequences of more than 200 nucleotides without a defined reading frame, belong to the regulatory non-coding RNA's family. Although their biological functions remain largely unknown, the number of these lncRNAs has steadily increased and it is now estimated that humans may have more than 10,000 such transcripts. Some of these are known to be involved in important regulatory pathways of gene expression which take place at the transcriptional level, but also at different steps of RNA co- and post-transcriptional maturation...
April 10, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29708511/prometheus-revisited
#19
Kai-Yuan Chen, Xiling Shen, Anna Mae Diehl
The liver's extraordinary ability to regenerate has been known since the myth of Prometheus, but the mechanisms involved are still being discovered. Various small animal models have been used in this quest. Two of the most popular include partial hepatectomy (PHx), in which two-thirds of the liver mass is surgically removed to evoke a massive, immediate stimulus for regeneration, and prolonged exposure to toxins that kill liver cells more gradually, provoking chronic regenerative activity. In either case, multiple types of cells must interact effectively to repopulate the organ with functional mature hepatocytes and thus assure ultimate restoration of healthy liver structure and function...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29706291/characterization-of-recombinant-yellow-fever-dengue-vaccine-viruses-with-human-monoclonal-antibodies-targeting-key-conformational-epitopes
#20
Valerie Lecouturier, Catherine Berry, Aure Saulnier, Sophie Naville, Catherine Manin, Yves Girerd-Chambaz, James E Crowe, Nicholas Jackson, Bruno Guy
The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several dengue-endemic countries. Although the vaccine provides protection against dengue, the level of protection differs by serotype and warrants further investigation. We characterized the antigenic properties of each vaccine virus serotype using highly neutralizing human monoclonal antibodies (hmAbs) that bind quaternary structure-dependent epitopes. Specifically, we monitored the binding of dengue virus-1 (DENV-1; 1F4), DENV-2 (2D22) or DENV-3 (5J7) serotype-specific or DENV-1-4 cross-reactive (1C19) hmAbs to the four chimeric yellow fever-dengue vaccine viruses (CYD-1-4) included in phase III vaccine formulations using a range of biochemical and functional assays (dot blot, ELISA, surface plasmon resonance and plaque reduction neutralization assays)...
April 26, 2018: Vaccine
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