Cryo-EM structure of the human native plasma coagulation factor XIII complex.

The structure of human coagulation factor XIII (FXIII), a heterotetrameric plasma pro-transglutaminase that covalently crosslinks pre-formed fibrin polymers, remains elusive until today. The heterotetrameric complex is composed of two catalytic FXIII-A and two protective FXIII-B subunits. Structural etiology underlying FXIII deficiency has so far been derived from crystallographic structures, all of which are currently available for the FXIII-A2 homodimer only.

Architectures of photosynthetic RC-LH1 supercomplexes from .

The reaction center-light-harvesting complex 1 (RC-LH1) plays an essential role in the primary reactions of bacterial photosynthesis. Here, we present high-resolution structures of native monomeric and dimeric RC-LH1 supercomplexes from () using cryo-electron microscopy. The RC-LH1 monomer is composed of an RC encircled by an open LH1 ring comprising 15 αβ heterodimers and a PufX transmembrane polypeptide.

In-depth structure-function profiling of the complex formation between clotting factor VIII and heme.

Background And Aims: Blood disorders, such as sickle cell disease, and other clinical conditions are often accompanied by intravascular hemolytic events along with the development of severe coagulopathies. Hemolysis, in turn, leads to the accumulation of Fe(II/III)-protoporphyrin IX (heme) in the intravascular compartment, which can trigger a variety of proinflammatory and prothrombotic reactions. As such, heme binding to the blood coagulation proteins factor VIII (FVIII), fibrinogen, and activated protein C with functional consequences has been demonstrated earlier.

Releasing Nonperipheral Subunits from Protein Complexes in the Gas Phase.

The quaternary structure is an important feature regulating protein function. Native mass spectrometry contributes to untangling quaternary structures by preserving the integrity of protein complexes in the gas phase. Tandem mass spectrometry by collision-induced dissociation (CID) can then be used to release subunits from these intact complexes, thereby providing structural information on the stoichiometry and topology.

Structural diversity in the atomic resolution 3D fingerprint of the titin M-band segment.

In striated muscles, molecular filaments are largely composed of long protein chains with extensive arrays of identically folded domains, referred to as "beads-on-a-string". It remains a largely unresolved question how these domains have developed a unique molecular profile such that each carries out a distinct function without false-positive readout. This study focuses on the M-band segment of the sarcomeric protein titin, which comprises ten identically folded immunoglobulin domains.

Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement.

Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo-electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1-immunoglobulin G1 (IgG1) hexamer complexes.

Molecular Basis of Assembly and Activation of Complement Component C1 in Complex with Immunoglobulin G1 and Antigen.

The classical complement pathway contributes to the natural immune defense against pathogens and tumors. IgG antibodies can assemble at the cell surface into hexamers via Fc:Fc interactions, which recruit complement component C1q and induce complement activation. Biophysical characterization of the C1:IgG complex has remained elusive primarily due to the low affinity of IgG-C1q binding.

Complement is activated by IgG hexamers assembled at the cell surface.

Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells.