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Structure of the extracellular domains of human and X enopus F n14: implications in the evolution of TWEAK and F n14 interactions
Author(s) -
Pellegrini Maria,
Willen Laure,
Perroud Mai,
Krushinskie Dennis,
Strauch Kathy,
Cuervo Hernan,
Day Eric S.,
Schneider Pascal,
Zheng Timothy S.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12206
Subject(s) - surface plasmon resonance , xenopus , binding site , homology modeling , protein–protein interaction , receptor , docking (animal) , plasma protein binding , chemistry , biology , microbiology and biotechnology , biochemistry , enzyme , gene , medicine , materials science , nursing , nanoparticle , nanotechnology
TWEAK ( TNF homologue with weak apoptosis‐inducing activity) and Fn14 (fibroblast growth factor‐inducible protein 14) are members of the tumor necrosis factor ( TNF ) ligand and receptor super‐families. Having observed that Xenopus Fn14 cross‐reacts with human TWEAK , despite its relatively low sequence homology to human Fn14, we examined the conservation in tertiary fold and binding interfaces between the two species. Our results, combining NMR solution structure determination, binding assays, extensive site‐directed mutagenesis and molecular modeling, reveal that, in addition to the known and previously characterized β−hairpin motif, the helix‐loop‐helix motif makes an essential contribution to the receptor/ligand binding interface. We further discuss the insight provided by the structural analyses regarding how the cysteine‐rich domains of the TNF receptor super‐family may have evolved over time. Database Structural data are available in the Protein Data Bank/BioMagResBank databases under the accession codes 2 KMZ , 2 KN 0 and 2 KN 1 and 17237, 17247 and 17252. Structured digital abstractTWEAK binds to hFn14 by surface plasmon resonance ( View interaction ) xeFn14 binds to TWEAK by enzyme linked immunosorbent assay ( View interaction ) TWEAK binds to xeFn14 by surface plasmon resonance ( View interaction ) hFn14 binds to TWEAK by enzyme linked immunosorbent assay ( View interaction )