The present disclosure relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present disclosure relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present disclosure can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.

The disclosure provides helix grafted proteins, methods of producing helix grafted proteins and methods of use of helix grafted proteins as inhibitors of protein-protein interactions involved in disease pathogenesis.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

The disclosure provides helix grafted proteins, methods of producing helix grafted proteins and methods of use of helix grafted proteins as inhibitors of protein-protein interactions involved in disease pathogenesis.

Methods, compositions and kits for regulating complement activity or treating a complement activity disorder in a subject using soluble, membrane-independent CD59 protein, methods of assaying human macular degeneration (MD), and methods and kits for assaying potential therapeutic agents for treatment of human MD are provided herein.

The present invention relates to peptides, methods for production of the same, nanoparticle formulations of the same and the use of these new peptides and nanoparticle formulations as inhibitors of protein-protein interactions, in particular for application in the treatment of diseases associated with overexpression of the RAN gene.

The present invention relates to peptides, methods for production of the same, nanoparticle formulations of the same and the use of these new peptides and nanoparticle formulations as inhibitors of protein-protein interactions, in particular for application in the treatment of diseases associated with overexpression of the RAN gene.

This application discloses microorganisms and methods of producing GNAQ/GNA11 inhibitors and methods of making antibody drug conjugates of anti-PMEL17 antibodies or antigen binding fragments conjugated to a GNAQ/GNA11 inhibitor. The disclosure also relates to formulations comprising antibody drug conjugates of anti-PMEL 17 antibodies or antigen binding fragments conjugated to a GNAQ/GNA1 inhibitor and methods of treating or preventing cancer using the formulations.

The invention provides a mutant of a parent heterotrimeric G protein alpha (G?) subunit, which mutant (i) lacks at least one helix of the helical domain of the parent G? subunit; (ii) is capable of binding to a GPCR in the absence of a heterotrimeric G protein beta (G?) subunit and a heterotrimeric G protein gamma (G?) subunit; and (iii) has an amino acid sequence that contains one or more mutations compared to the amino acid sequence of the parent heterotrimeric G? subunit, which mutations are selected from a deletion, a substitution and an insertion.

Provided herein are compounds that inhibit a binding interaction between a integrin and a G protein subunit, as well as compositions, e.g., pharmaceutical compositions, comprising the same, and related kits. In some embodiments, the compound is an antibody or antibody analog, and, in other embodiments, the compound is a peptide or peptide analog. Also provided are methods of using the compounds, including methods of treating or preventing a medical condition, such as stroke, heart attack, cancer, or inflammation.