Marco Mattu

TL;DR: The structure clarifies the role of active‐ site residues in the deacetylation reaction and substrate recognition and shows the unexpected role of a conserved residue at the active‐site rim, Asp 101, in positioning the substrate by directly interacting with the peptidic backbone and imposing a constrained cis‐conformation.

TL;DR: The results of the biochemical and cell-based experiments suggest a model in which secreted PCSK9 binds to LDLR and directs the trafficking of LDLR to the lysosomes for degradation.

TL;DR: The finding that the D5 fusion-inhibitory antibody shares the same binding site suggests that the hydrophobic pocket is a "hot spot" for fusion inhibition and an ideal target on which to focus a vaccine-elicited antibody response.

TL;DR: It is found that although the EGF(AB)H306Y-PCSK9 interaction is pH-independent, LDLRH306Y binds PCSK 9 50-fold better at low pH, suggesting that factors other than His-306 contribute to the pH dependence of PCSK9-LDLR binding.

TL;DR: The 2.0-Å-resolution crystal structure of the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules is reported.