For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
9
views
17
references
 Top references
cited by
62
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      437
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers.

          Related collections

          Most cited references17

          • Record: found
          • Abstract: found
          • Article: not found

          Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids.

          GREGG FIELDS, RICHARD L. NOBLE (1990)
          9-Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been greatly enhanced by the introduction of a variety of solid supports, linkages, and side chain protecting groups, as well as by increased understanding of solvation conditions. These advances have led to many impressive syntheses, such as those of biologically active and isotopically labeled peptides and small proteins. The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly "orthogonal" scheme, and thus offers many unique opportunities for bioorganic chemistry.
          Article 0 comments Cited 193 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Benchmarking fold detection by DaliLite v.5

            Liisa Holm, Arne Elofsson (2019)
            Protein structure comparison plays a fundamental role in understanding the evolutionary relationships between proteins. Here, we release a new version of the DaliLite standalone software. The novelties are hierarchical search of the structure database organized into sequence based clusters, and remote access to our knowledge base of structural neighbors. The detection of fold, superfamily and family level similarities by DaliLite and state-of-the-art competitors was benchmarked against a manually curated structural classification. Database search strategies were evaluated using Fmax with query-specific thresholds. DaliLite and DeepAlign outperformed TM-score based methods at all levels of the benchmark, and DaliLite outperformed DeepAlign at fold level. Hierarchical and knowledge-based searches got close to the performance of systematic pairwise comparison. The knowledge-based search was four times as efficient as the hierarchical search. The knowledge-based search dynamically adjusts the depth of the search, enabling a trade-off between speed and recall. http://ekhidna2.biocenter.helsinki.fi/dali/README.v5.html. Supplementary data are available at Bioinformatics online.
            Article 0 comments Cited 137 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement.

              Deniz Ugurlar, Piet Gros, Paul Parren … (2018)
              Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo-electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1-immunoglobulin G1 (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc-CH2 domains of each IgG molecule. These are consistent with known interactions and also reveal additional interactions, which are supported by functional IgG1-mutant analysis. Upon antibody binding, the C1q arms condense, inducing rearrangements of the C1r2s2 proteases and tilting C1q's cone-shaped stalk. The data suggest that C1r may activate C1s within single, strained C1 complexes or between neighboring C1 complexes on surfaces.
              Article 0 comments Cited 74 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Science
                Abbreviated Title: Science
                Publisher: American Association for the Advancement of Science (AAAS)
                ISSN (Print): 0036-8075
                ISSN (Electronic): 1095-9203
                Publication date Created: March 12 2020
                Publication date Created: March 13 2020
                Publication date (Print): March 13 2020
                Publication date (Electronic): February 20 2020
                Volume: 367
                Issue: 6483
                Pages: 1224-1230
                Affiliations
                [1 ]Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA.
                [2 ]Department of Antibody Engineering, Genentech Inc., South San Francisco, CA 94080, USA.
                [3 ]Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA 94080, USA.
                [4 ]Department of Biomolecular Resources, Genentech Inc., South San Francisco, CA 94080, USA.
                [5 ]Cambridge Institute for Medical Research, University of Cambridge, Keith Peters Building, Cambridge CB2 0XY, UK.
                Article
                DOI: 10.1126/science.aaz9356
                PubMed ID: 32079680
                SO-VID: 53135974-fdd0-46e4-b2aa-84cb979e057d
                Copyright © © 2020
                License:

                http://www.sciencemag.org/about/science-licenses-journal-article-reuse

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content437

                See all similar

                Cited by65

                See all cited by

                Most referenced authors868

                See all reference authors