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PDBsum entry 2f83
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the factor XI zymogen reveals a pathway for transactivation.
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Authors
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E.Papagrigoriou,
P.A.Mcewan,
P.N.Walsh,
J.Emsley.
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Ref.
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Nat Struct Mol Biol, 2006,
13,
557-558.
[DOI no: ]
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PubMed id
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Abstract
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Factor XI (FXI), a coagulation protein essential to normal hemostasis,
circulates as a disulfide-linked dimer. Here we report the full-length FXI
zymogen crystal structure, revealing that the protease and four apple domains
assemble into a unique 'cup and saucer' architecture. The structure shows that
the thrombin and platelet glycoprotein Ib binding sites are remote within the
monomer but lie in close proximity across the dimer, suggesting a
transactivation mechanism.
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Figure 1.
Figure 1. FXI structure. (a) Topology of the four apple
domains is represented with the protease domain removed.
Connecting loops are colored black and the loop after A4, which
leads to the C-terminal protease domain, is colored dark blue.
(b) Topology of the FXI dimer with the protease domain colored
red and Cys321 disulfide located centrally. (c) Two close-up
views of the A4 dimer interface related by a 90° rotation.
Left, interacting side chains from one side of the dimer
interface are colored yellow, making contact with a
charge-surface representation of the other half of the interface
(blue, positive; red, negative). Right, a ribbon diagram shows a
rotated view of the A4 dimer with hydrogen bonds and
electrostatic interactions colored orange.
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Figure 2.
Figure 2. FXI activation. (a) Ribbon diagrams representing
zymogen activation by superposition of the FXIa structure
(green; PDB entry 1ZJD) and the zymogen protease domain
(yellow). The region of largest conformation change is the
activation loop comprising residues 376–370. Ile370 side chain
is colored purple in both structures. Active site Ser557 side
chain is also shown. (b) Space-filling representation of the FXI
dimer. White side chains, Arg369 and Ile370 from the activation
loop; blue side chain, Lys252 and Lys253; red side chain, Glu66.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
557-558)
copyright 2006.
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