Antibody-mediated neutralisation of Gremlin-1 was ineffective in treating fibrosis in metabolic dysfunction-associated steatohepatitits, likely due to low hepatic expression in a subset of myofibroblasts and redundant Gremlin-1 signalling.
Samantha Wellington Miranda, Qian Cong ... E Peter Greenberg
The extension of covariation analyses to proteins that coevolve but do not physically interact enabled identification of selectivity residues in quorum sensing proteins, providing insight into the evolution of signaling systems.
A new method of protein structure prediction that incorporates residue–residue co-evolution information into the Rosetta structure prediction program was used to develop models for 58 large protein families that had no previous structural information.
Sergey Ovchinnikov, Hetunandan Kamisetty, David Baker
Co-evolving residue pairs in the different components of a protein complex almost always make contact across the protein–protein interface, thus providing powerful restraints for the modeling of protein complexes.
Paul Knabl, Alexandra Schauer ... Grigory Genikhovich
ChIP-seq analysis reveals BMP signaling targets in a cnidarian and identifies ZSWIM4-6 as a dampener of the pSMAD1/5 gradient and a potential conveyor of the BMP-mediated gene repression.
Experimental determination of residue contacts from mutational data allows model discrimination and identification of in vivo functional conformations of proteins.
Molly C Sutherland, Deanna L Mendez ... Robert G Kranz
Despite the known heme attachment motif (CXXCH) in all c-type cytochromes, attachment elements recognized by human and bacterial cytochrome c biogenesis pathways are distinct, providing clear targets for differential inhibitors.
Thuy-Lan V Lite, Robert A Grant ... Michael T Laub
A generalizable approach to understanding the logic of molecular recognition reveals the contributions of individual residues to the specificity of protein-protein interactions.