Crystal structure of coagulation factor XII N-terminal domains 1–5

Saleem, M.; Li, C.; Kaira, B.G.; Brown, A.K.; Pathak, M.; Najmudin, S.; Cowieson, N.; Dreveny, I.; Wilson, C.; Shamanaev, A.; Gailani, D.; Smith, S.A.; Morrissey, J.H.; Philippou, H.; Emsley, J.

doi:10.1107/S2059798325005297

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Figure 1
FXII function and FXII^HC5 structure. (a) Contact activation is illustrated, whereby the recognition of endogenous negatively charged polymers by FXII results in reciprocal activation with prekallikrein (PK) in complex with high-molecular-weight kininogen (HK). The active enzymes trigger proteolytic cascades, resulting in inflammatory and thrombotic responses. (b) Schematic diagram showing the domain organization of the FXII polypeptide with the FnII domain in blue, EGF1 in green, FnI in orange, EGF2 in black, kringle in red and PRR and protease domain in white. Residue numbers are shown under each domain. (c) Cartoon diagram of the crystal structure of the FXII^HC5 monomer revealing a torc shape. (d) The FnII and kringle domains form a head-to-tail intramolecular interaction, with key residues shown as sticks and electrostatic interactions shown as dashed lines. Residues from the cation-binding site (FnII) and the lysine-binding site (kringle) are shown as sticks. (e) Schematic diagram showing the dimer domain organization of the FXII^HC5 structure. (f) Cartoon diagram showing the FXII^HC5 dimer structure as two interlocking torc shapes, resulting in a triangular shape with close relative positioning of the kringle domains and distant spatial separation of the two FnII domains.

STRUCTURAL
BIOLOGY

ISSN: 2059-7983

Volume 81| Part 7| July 2025| Pages 380-393

https://doi.org/10.1107/S2059798325005297

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