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High Molecular Weight Kininogen: A Review of the Structural Literature

Journal

Publisher

MDPI
DOI: 10.3390/ijms222413370

Keywords

kininogen; structure; AlphaFold; cryo-EM; proteins; kinin; bradykinin

Funding

  1. NIH [P41 RR001081]

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Kininogens are multidomain glycoproteins with important roles in the intrinsic pathway of coagulation and the generation of the vasoactive peptide bradykinin. Despite previous failures to crystallize kininogen, new advancements in cryo-electron microscopy offer opportunities to study its structure at an atomic level.
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.

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