scholarly journals The structural basis for high‐affinity uptake of lignin‐derived aromatic compounds by proteobacterial TRAP transporters

FEBS Journal ◽  
2021 ◽  
Author(s):  
Claudine Bisson ◽  
Robert C. Salmon ◽  
Laura West ◽  
John B. Rafferty ◽  
Andrew Hitchcock ◽  
...  
Keyword(s):  
Aromatic Compounds ◽  
Structural Basis ◽  
High Affinity ◽  
High Affinity Uptake

scholarly journals The Structural Basis of Repertoire Shift in an Immune Response to Phosphocholine

2000 ◽  
Vol 191 (12) ◽  
pp. 2101-2112 ◽  
Author(s):  
McKay Brown ◽  
Maria A. Schumacher ◽  
Gregory D. Wiens ◽  
Richard G. Brennan ◽  
Marvin B. Rittenberg
Keyword(s):  
Immune Response ◽  
Light Chain ◽  
Indirect Effects ◽  
Somatic Mutations ◽  
Variable Region ◽  
Primary Response ◽  
Structural Basis ◽  
Antibody Repertoire ◽  
High Affinity

The immune response to phosphocholine (PC)–protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high affinity to PC–protein. The somatically mutated memory hybridoma, M3C65, possesses high affinity for PC–protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine (NPPC). Affinity measurements using related PC–phenyl analogues, including peptides of varying lengths, demonstrate that carrier determinants contribute to binding affinity and that somatic mutations alter this recognition. The crystal structure of an M3C65–NPPC complex at 2.35-Å resolution allows evaluation of the three light chain mutations that confer high-affinity binding to NPPC. Only one of the mutations involves a contact residue, whereas the other two have indirect effects on the shape of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural evidence for the role of carrier determinants in promoting repertoire shift. These two antibodies express unrelated variable region heavy and light chain genes and represent a classic example of the effect of repertoire shift on maturation of the immune response.

High affinity uptake of neurotransmitter amino acids (reply)

Nature ◽  
1975 ◽  
Vol 253 (5491) ◽  
pp. 481-482 ◽  
Author(s):  
LEVI ◽  
RAITERI
Keyword(s):  
Amino Acids ◽  
Neurotransmitter Amino Acids ◽  
High Affinity ◽  
High Affinity Uptake

scholarly journals The human organic cation transporter OCT1 mediates high affinity uptake of the anticancer drug daunorubicin

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Emil Andreev ◽  
Nicolas Brosseau ◽  
Euridice Carmona ◽  
Anne-Marie Mes-Masson ◽  
Dindial Ramotar
Keyword(s):  
Anticancer Drug ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
High Affinity ◽  
High Affinity Uptake

scholarly journals SARS-CoV-2 RBD in vitro evolution parrots and predicts contagious mutation spread

2021 ◽  
Author(s):  
Gideon Schreiber ◽  
Jiri Zahradník ◽  
Shir Marciano ◽  
Maya Shemesh ◽  
Eyal Zoler ◽  
...  
Keyword(s):  
South African ◽  
Convergent Evolution ◽  
Vaccine Development ◽  
Spike Protein ◽  
Structural Basis ◽  
Receptor Binding Domain ◽  
In Vitro Evolution ◽  
High Affinity ◽  
Future Drug

Abstract SARS-CoV-2 is continually evolving, with more contagious mutations spreading rapidly. Using in vitro evolution to affinity maturate the receptor-binding domain (RBD) of the spike protein towards ACE2 resulted in the more contagious mutations, S477N, E484K, and N501Y, to be among the first selected, explaining the convergent evolution of the “European” (20E-EU1), “British” (501.V1),”South African” (501.V2), and Brazilian variants (501.V3). Plotting the binding affinity to ACE2 of all RBD mutations against their incidence in the population shows a strong correlation between the two. Further in vitro evolution enhancing binding by 600-fold provides guidelines towards potentially new evolving mutations with even higher infectivity. For example, Q498R epistatic to N501Y. Nevertheless, the high-affinity RBD is also an efficient drug, inhibiting SARS-CoV-2 infection. The 2.9Å Cryo-EM structure of the high-affinity complex, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.

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