Publications by authors named "Dennis Vestergaard Pedersen"
Article Synopsis
- Tarperprumig (ALXN1820) is a bispecific antibody designed to treat conditions caused by dysregulated activity in the complement alternative pathway, usable via small volume injections either under the skin or intravenously.
- It consists of two variable domains that target properdin and human serum albumin, showing a high binding affinity and forming a stable complex.
- The antibody effectively inhibits key processes related to complement pathway activation and is currently undergoing clinical development for relevant disorders.
Article Synopsis
- Gefurulimab (ALXN1720) is a bispecific antibody designed for subcutaneous treatment of chronic disorders linked to the activation of the terminal complement pathway by blocking the breakdown of complement component 5 (C5).
- It consists of specialized antibody fragments derived from llamas and humans that bind tightly to C5 and human serum albumin (HSA), enabling it to inhibit complement activity effectively in lab assays.
- Structural studies indicate that gefurulimab obstructs C5's interaction with its activating convertase, suggesting it is a strong candidate for treating complement-mediated disorders.
The complement system which is part of the innate immune response against invading pathogens represents a powerful mechanism for killing of infected cells. Utilizing direct complement recruitment for complement-mediated elimination of HIV-1-infected cells is underexplored. We developed a novel therapeutic modality to direct complement activity to the surface of HIV-1-infected cells.
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- Researchers developed a method to stabilize labile macromolecular complexes by using peptide tags and nanobodies to prevent dissociation during crystallization or electron microscopy preparation.
- This technique enabled them to determine the crystal structure of a large 320 kDa proconvertase complex with a high resolution of 3.9 Å.
- The study highlights the importance of specific structural features in properdin for enhancing C3 convertase activity and suggests that this nanobody bridging approach could be valuable for studying other unstable complexes in biochemistry.
Article Synopsis
- - Structures of alternative pathway proteins, particularly properdin (FP), provide insights into how they activate and regulate the complement cascade's amplification pathway, crucial for immune responses.
- - Recent advancements have revealed details about FP and its interactions with C3b and factor B, helping to explain how FP's function is influenced by its oligomerization state and the impact of mutations that cause FP deficiency.
- - The review also covers how FP is inhibited by tick proteins, discusses the potential of AI predictions for studying FP's interactions with other proteins, and highlights the implications for understanding diseases related to low FP levels.
Crystallization and X-ray analysis of monodisperse human properdin.
Acta Crystallogr F Struct Biol Commun
February 2019
The 54 kDa protein properdin, also known as factor P (FP), plays a major role in the complement system through the stabilization of the alternative pathway convertases. FP circulates in the blood as cyclic dimers, trimers and tetramers, and this heterogeneity challenges detailed structural insight into the mechanism of convertase stabilization by FP. Here, the generation of an intact FP monomer and a variant monomer with the third thrombospondin repeat liberated is described.
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