The ERVK3-1 Microprotein Interacts with the HUSH Complex.

Human endogenous retroviruses (hERVs) are noninfectious molecular remnants of ancient exogenous retroviruses that now make up 8% of the human genome. The ubiquitously expressed human locus was recently annotated as encoding a 109-amino acid endogenous retroviral Rec microprotein. However, because this locus was thought to be noncoding until recently, it is currently unknown whether the ERVK3-1 microprotein has a function in human cells.

Eukaryotic Microproteins.

Microproteins are polypeptides of 100-150 amino acids or fewer that have not been annotated by genome annotation consortia, given their small size and other noncanonical properties. Translated microproteins are now known to number in the thousands in the human genome, to function in critical cellular and physiological processes, and to be dysregulated or mutated in diseases including neurodegeneration and cancer. Knowledge about microproteins has rapidly accumulated since the advent of ribosome profiling enabled their global discovery 15 years ago.

Discovery of first-in-class nanomolar inhibitors of heptosyltransferase I reveals a new aminoglycoside target and potential alternative mechanism of action.

A clinically relevant inhibitor for Heptosyltransferase I (HepI) has been sought after for many years because of its critical role in the biosynthesis of lipopolysaccharides on bacterial cell surfaces. While many labs have discovered or designed novel small molecule inhibitors, these compounds lacked the bioavailability and potency necessary for therapeutic use. Extensive characterization of the HepI protein has provided valuable insight into the dynamic motions necessary for catalysis that could be targeted for inhibition.