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Evolutionary conservation of the allosteric activation of factor VII a by tissue factor in lamprey
Author(s) -
Beeler D. L.,
Aird W. C.,
Grant M. A.
Publication year - 2018
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13968
Subject(s) - allosteric regulation , lamprey , tissue factor , chemistry , computational biology , biology , biochemistry , coagulation , receptor , medicine , fishery
Essentials Tissue factor (TF) enhances factor VIIa (FVIIa) activity through structural and dynamic changes. We analyzed conservation of TF‐activated FVIIa allosteric networks in extant vertebrate lamprey. Lamprey Tf/FVIIa molecular dynamics show conserved Tf‐induced structural/dynamic FVIIa changes. Lamprey Tf activation of FVIIa allosteric networks follows molecular pathways similar to human.Summary Background Previous studies have provided insight into the molecular basis of human tissue factor ( TF ) activation of activated factor VII ( FVII a). TF ‐induced allosteric networks of FVII a activation have been rationalized through analysis of the dynamic changes and residue connectivities in the human soluble TF ( sTF )/ FVII a complex structure during molecular dynamics ( MD ) simulation. Evolutionary conservation of the molecular mechanisms for TF ‐induced allosteric FVII a activation between humans and extant vertebrate jawless fish (lampreys), where blood coagulation emerged more than 500 million years ago, is unknown and of considerable interest. Objective To model the sT f/ FVII a complex from cloned Petromyzon marinus lamprey sequences, and with comparisons to human sTF / FV lla investigate conservation of allosteric mechanisms of FVII a activity enhancement by soluble TF using MD simulations. Methods Full‐length cDNA s of lamprey tf and f7 were cloned and characterized. Comparative models of lamprey sT f/ FVII a complex and free FVII a were determined based on constructed human sTF / FVII a complex and free FVII a models, used in full‐atomic MD simulations, and characterized using dynamic network analysis approaches. Results Allosteric paths of correlated motion from Tf contact points in lamprey sT f/ FVII a to the FVII a active site were determined and quantified, and were found to encompass residue–residue interactions along significantly similar paths compared with human. Conclusions Despite low conservation of residues between lamprey and human proteins, 30% TF and 39% FVII , the structural and protein dynamic effects of TF activation of FVII a appear conserved and, moreover, present in extant vertebrate proteins from 500 million years ago when TF / FVII a‐initiated extrinsic pathway blood coagulation emerged.