Abstract
Kininogens are multidomain glycoproteins found in the blood of most vertebrates. High molecular weight kininogen demonstrate both carrier and co-factor activity as part of the intrinsic pathway of coagulation, leading to thrombin generation. Kininogens are the source of the vasoactive nonapeptide bradykinin. To date, attempts to crystallize kininogen have failed, and very little is known about the shape of kininogen at an atomic level. New advancements in the field of cryo-electron microscopy (cryoEM) have enabled researchers to crack the structure of proteins that has been refractory to traditional crystallography techniques. High molecular weight kininogen is a good candidate for structural investigation by cryoEM. The goal of this review is to summarize the findings of kininogen structural studies.
Highlights
Kininogens or Fitzgerald factors are multidomain glycoproteins found in the blood of most vertebrates [1,2,3,4]
Kininogens have been studied for decades, the atomic arrangement of full length kininogen or its fragments are still unknown for all species with no coordinates in Protein Data Bank (PDB)
Perhaps what the authors of this study showed were not individual kininogen molecules, but rather their aggregates, where a single domain is one kininogen molecule
Summary
Kininogens or Fitzgerald factors are multidomain glycoproteins found in the blood of most vertebrates [1,2,3,4]. Together with coagulation factor (f)XI, the KKS form the contact activation system of blood coagulation (CAS) or more commonly known as the intrinsic pathway of coagulation contributing to thrombin generation primarily under pathologic conditions. A protein Basic Local Alignment Search Tool (BlastP) applied with human kininogen amino acid sequence against PDB returns only proteins containing homologous cystatin domains with identity around 30% (Table 1). Entering the keyword “kininogen” in the database search engine returns only structures containing polypeptide fragments referred to as “inserts of kininogen peptides”,. Contact pathway inhibitor from a sand fly Backbone structure of Des-Arg10-Kallidin (DAKD) peptide bound to human Bradykinin 1 Receptor (B1R) determined by DNP-enhanced. Backbone structure of free bradykinin (BK) in DDM/CHS detergent micelle determined by MAS SSNMR
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