X-ray crystal structure of the fibrinolysis inhibitor alpha2-antiplasmin.
The serpin alpha(2)-antiplasmin (SERPINF2) is the principal inhibitor of plasmin and inhibits fibrinolysis. Accordingly, alpha(2)-antiplasmin deficiency in humans results in uncontrolled fibrinolysis and a bleeding disorder. alpha(2)-antiplasmin is an unusual serpin, in that it contains extensive N- and C-terminal sequences flanking the serpin domain. The N-terminal sequence is crosslinked to fibrin by factor XIIIa, whereas the C-terminal region mediates the initial interaction with plasmin. To understand how this may happen, we have determined the 2.65A X-ray crystal structure of an N-terminal truncated murine alpha(2)-antiplasmin. The structure reveals that part of the C-terminal sequence is tightly associated with the body of the serpin. This would be anticipated to position the flexible plasmin-binding portion of the C-terminus in close proximity to the serpin Reactive Center Loop where it may act as a template to accelerate serpin/protease interactions.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
Ruby H P
RH
Law
Trifina
T
Sofian
Wan-Ting
WT
Kan
Anita J
AJ
Horvath
Corinne R
CR
Hitchen
Christopher G
CG
Langendorf
Ashley M
AM
Buckle
James C
JC
Whisstock
Paul B
PB
Coughlin
D000818:Animals; D000933:Antifibrinolytic Agents / Q000737:chemistry; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000979:alpha-2-Antiplasmin / Q000737:chemistry* / Q000235:genetics
D000933:Antifibrinolytic Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin