Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: The present invention relates to the field of affinity purification and provides for means and methods applying protein binding agents competing for a target protein for use as capture and elution tool, wherein the elution agent comprises an immunoglobulin single variable domain (ISVD), and is capable of displacing the capturing binding agent. More specifically, the displacement efficiency of the ISVD-containing protein binding agent is driven by its dissociation kinetics, with a rate constant of dissociation (koff) equal or lower as compared to the capturing agent. Furthermore, said protein binding agents are deployable in high-throughput purification from complex mixtures, or for capturing protein-complexes, thereby facilitating structural, biochemical and physicochemical analysis of said target proteins.

Abstract: The present invention relates to the field of structural biology. More specifically, the present invention relates to novel antigen-binding chimeric proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use as a therapeutic, diagnostic, or imaging tool. Even more specifically, the invention relates to a fusion of a scaffold protein and an antigen-binding domain wherein the scaffold protein of said fusion interrupts the Immunoglobulin domain topology to form a rigid chimer.

Abstract: The disclosure relates cells or cellular systems that express both a membrane protein and a binding domain directed to the membrane protein. Also, methods are provided that use such cells or cellular systems to produce higher amounts of the membrane proteins. Further, the cells or cellular systems can be used as tools for the structural and functional characterization of membrane proteins, as well as for screening and drug discovery efforts targeting membrane proteins.

Abstract: The present invention relates to non-naturally occurring antibodies or active antibody fragments specifically binding the calcium-sensing receptor (CaSR), acting as positive allosteric modulators (PAMs) to provide for potent therapeutic agents. More particular, the immunoglobulin single variable domains (ISVDs) identified herein reveal a novel therapeutic strategy to reduce parathyroid hormone release in a subject, and are therefore suitable for treatment of hypercalcemia disorders. Moreover, co-application of such an ISVD and a synthetic PAM or calcimimetic results in a synergistic agonistic CaSR activity providing for pharmaceutical compositions as next generation CaSR drugs.

Abstract: The disclosure relates cells or cellular systems that express both a membrane protein and a binding domain directed to the membrane protein. Also, methods are provided that use such cells or cellular systems to produce higher amounts of the membrane proteins. Further, the cells or cellular systems can be used as tools for the structural and functional characterization of membrane proteins, as well as for screening and drug discovery efforts targeting membrane proteins.

Abstract: The present invention relates to binding agents specific for the cystic fibrosis transmembrane conductance regulator (CFTR), which increase its thermal stability to provide for potent therapeutics. More particular, the immunoglobulin single variable domains (ISVDs) identified herein reveal novel binding sites on the nucleotide-binding domain 1 of CFTR, which allow to rescue pathogenic mutant F508del CFTR from proteasomal degradation. The binding agents are therefore considered suitable in treatment of cystic fibrosis. Finally, also crystalline structures demonstrating binding interfaces, and computer-assisted methods for selecting molecules able to stabilize CFTR are described.

Abstract: Agents that specifically bind to an opioid receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure-based drug design.

Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: The present invention relates to the field of structural biology and drug discovery. More specifically, the present invention relates to novel fusion proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use in structure-based drug design and screening, and as pharmacological tools. Even more specifically, the invention relates to a functional fusion of a toxin and a scaffold protein wherein the folded scaffold protein interrupts the topology of the toxin by insertion in an exposed ?-turn of a ?-strand-containing domain of said toxin to form a rigid fusion protein that retains its high affinity target binding capacity.

Abstract: The present invention relates to the field of structural biology. More specifically, the present invention relates to novel fusion proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use in structure-based drug design and screening. Even more specifically, the invention relates to a functional fusion protein of a cytokine and a scaffold protein wherein the scaffold is a folded protein that interrupts the topology of the cytokine to form a rigid fusion protein that retains its receptor binding and activation capacity. More specifically, chemokine- and interleukin-based functional fusion proteins, and their production and uses, are disclosed herein.

Abstract: Agents that specifically bind to a muscarinic acetylcholine receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure based drug design.

Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: The present invention relates to the field of structural biology. More specifically, the present invention relates to novel antigen-binding chimeric proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use as a therapeutic, diagnostic, or imaging tool. Even more specifically, the invention relates to a fusion of a scaffold protein and an antigen-binding domain wherein the scaffold protein of said fusion interrupts the Immunoglobulin domain topology to form a rigid chimer.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Abstract: The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.