Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab

Science ◽  
2020 ◽  
Vol 367 (6483) ◽  
pp. 1224-1230 ◽  
Author(s):  
Lionel Rougé ◽  
Nancy Chiang ◽  
Micah Steffek ◽  
Christine Kugel ◽  
Tristan I. Croll ◽  
...  
Keyword(s):  
Structural Model ◽  
Structure And Function ◽  
Antigen Binding ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Therapeutic Monoclonal Antibody ◽  
Cross Links ◽  
Cell Membrane Protein ◽  
And Function ◽  
Cluster Of Differentiation

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.

Tyrosine Cross-Links:  Molecular Basis of Gluten Structure and Function

2001 ◽  
Vol 49 (5) ◽  
pp. 2627-2632 ◽  
Author(s):  
Katherine A. Tilley ◽  
Rachel E. Benjamin ◽  
Katherine E. Bagorogoza ◽  
B. Moses Okot-Kotber ◽  
Om Prakash ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Structure And Function ◽  
Cross Links ◽  
And Function ◽  
Gluten Structure

Structure-function investigation of a deoxyribozyme with dual chelatase and peroxidase activities

2004 ◽  
Vol 76 (7-8) ◽  
pp. 1537-1545 ◽  
Author(s):  
H.-W. Lee ◽  
D. J.-F. Chinnapen ◽  
D. Sen
Keyword(s):  
In Vitro Selection ◽  
Structural Model ◽  
Random Sequence ◽  
Structure And Function ◽  
Dna Library ◽  
Dna Molecule ◽  
Folded Structure ◽  
And Function ◽  
Porphyrin Metallation

PS2.M, an 18-nucleotide DNA molecule, has been shown to be a dual enzyme for porphyrin metallation and, when complexed with hemin, for peroxidation. To date, detailed information has not been available on either the actively folded structure of PS2.M or on the contribution of specific nucleotides within it toward the peroxidase activity. Here, we report a variety of experiments that probe the structure and function of PS2.M as well as of a number of point mutants of PS2.M. Based on these experiments, a structural model for the folding of PS2.M and the location of a functionally relevant hemin-binding site are proposed. A key finding is that PS2.M, originally obtained by in vitro selection from a random-sequence DNA library, is uniquely suited for its catalysis of peroxidation; all point mutants examined showed significantly poorer catalytic activity than PS2.M itself.

scholarly journals THE FINE STRUCTURE AND FUNCTION OF THE CONTRACTILE AXOSTYLES OF CERTAIN FLAGELLATES

1965 ◽  
Vol 24 (3) ◽  
pp. 387-400 ◽  
Author(s):  
A. V. Grimstone ◽  
L. R. Cleveland
Keyword(s):  
Plasma Membrane ◽  
Fine Structure ◽  
Structure And Function ◽  
Basal Bodies ◽  
Structural Components ◽  
Cross Links ◽  
Cilia And Flagella ◽  
Fine Structure And Function ◽  
And Function ◽  
Regular Arrays

The axostyles of the flagellates Oxymonas, Saccinobaculus, and Notila are large ribbon-shaped structures which undulate actively in the cytoplasm. The form of their movements is described and illustrated. Axostyles consist of regular arrays of longitudinal fibres, the number of which varies between 100 and 5000 in different species. The fibres are about 240 A in diameter, apparently hollow, regularly cross-banded with a periodicity of about 150 A, and connected by delicate cross-links, also at regular intervals of about 150 A. They resemble very closely the central fibres of cilia and flagella. No other structural components are present, except at the anterior end, where the fibres are attached to one or more basal bodies, and at the posterior tip, where they are anchored to the plasma membrane. The relevance of the findings to an understanding of the mechanism of ciliary and flagellar movements is discussed.

Structure and Function in Rhodopsin:  Effects of Disulfide Cross-Links in the Cytoplasmic Face of Rhodopsin on Transducin Activation and Phosphorylation by Rhodopsin Kinase†,‡

Biochemistry ◽  
1999 ◽  
Vol 38 (39) ◽  
pp. 12893-12898 ◽  
Author(s):  
Kewen Cai ◽  
Judith Klein-Seetharaman ◽  
John Hwa ◽  
Wayne L. Hubbell ◽  
H. Gobind Khorana
Keyword(s):  
Structure And Function ◽  
Cytoplasmic Face ◽  
Rhodopsin Kinase ◽  
Cross Links ◽  
And Function

scholarly journals The contribution of mutant amino acids to alloantigenicity.

1989 ◽  
Vol 170 (3) ◽  
pp. 739-750 ◽  
Author(s):  
J Bill ◽  
F Ronchese ◽  
R N Germain ◽  
E Palmer
Keyword(s):  
Amino Acid ◽  
Structural Model ◽  
Structure And Function ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Beta Chain ◽  
Alpha Helices ◽  
The Third ◽  
And Function ◽  
The Relationship

The I-Abm12 mutation has been used extensively to study the relationship between structure and function of murine class II major histocompatibility molecules. I-Abm12 differs from I-Ab by three amino acid replacements in the A beta chain, and the proposed structural model of the I-Abm12 molecule places these three amino acid substitutions along one of the alpha-helices where they may affect both antigen and TCR binding. Two of the substitutions, Ile----Phe67 and Thr----Lys71, are thought to point into the binding site, whereas the third substitution, Arg----Gln70, is thought to point up and hence, be available for binding to the TCR. These predicted orientations are consistent with serologic analysis of the bm12 molecule, which demonstrates that residue 70 is uniquely accessible to mAbs distinguishing I-Ab from I-Abm12. In this study we have determined the influence of each of these amino acid substitutions on the ability of the resulting molecules to stimulate a panel of I-Abm12 (allo) reactive T cell hybridomas. Our experiments indicate that reversion of the amino acid at position 70 from Gln (I-Abm12) to Arg (I-Ab) interferes with allorecognition by 33 of 35 I-Abm12-reactive hybridomas. On the other hand, many hybrids can tolerate amino acid substitutions at positions 67 or 71. Single amino acid substitutions at position 67, 70, or 71 are recognized by only a minority of I-Abm12-specific hybrids and usually the reactivity is greatly diminished. These data are most consistent with the idea that the amino acid at position 70 directly interacts with the TCR during allorecognition. The additional effects of residues 67 and 71 are consistent with a contribution by bound peptide to the allorecognition process.

Structure and Function of Escherichia Coli Ribosomal Protein L7/L12: Effect of Cross-Links and Deletions

1993 ◽  
pp. 521-532 ◽  
Author(s):  
Robert R. Traut ◽  
Andrew V. Oleinikov ◽  
Evgeny Makarov ◽  
George Jokhadze ◽  
Bertrand Perroud ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Ribosomal Protein ◽  
Structure And Function ◽  
Cross Links ◽  
And Function
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