Evidence map›Paper›PMID 39549835›Full record

ArticleJournal of thrombosis and haemostasis : JTH2025

Biophysical characterization of blood coagulation factor VIII binding to lipid nanodiscs that mimic activated platelet surfaces.

Nathan G Avery, Isabelle R Young, Selena Lu, Jordan D Vaughan, Patrick S Korus, Tera N Richardson, Kenneth C Childers, Serge L Smirnov, P Clint Spiegel

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. The Mirage of Factor Equivalence: Examining the Complexities of Non-Factor Therapies in Haemophilia.Haemophilia : the official journal of the World Federation of Hemophilia · 2025
    Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Nathan G AveryChemistry Department, Western Washington University, Bellingham, Washington, USA.
Isabelle R YoungChemistry Department, Western Washington University, Bellingham, Washington, USA.
Selena LuChemistry Department, Western Washington University, Bellingham, Washington, USA.
Jordan D VaughanChemistry Department, Western Washington University, Bellingham, Washington, USA.
Patrick S KorusChemistry Department, Western Washington University, Bellingham, Washington, USA.
Tera N RichardsonChemistry Department, Western Washington University, Bellingham, Washington, USA.
Kenneth C ChildersChemistry Department, Western Washington University, Bellingham, Washington, USA.
Serge L SmirnovChemistry Department, Western Washington University, Bellingham, Washington, USA.
P Clint SpiegelChemistry Department, Western Washington University, Bellingham, Washington, USA. Electronic address: Paul.Spiegel@wwu.edu.

Funding

Unraveling the immune response to factor VIIIU54HL141981 · NHLBI · EMORY UNIVERSITY · PI DOERING, CHRISTOPHER BRADLEY · 2018 to 2022
$8.1M
Structural and Biochemical Studies of Blood Coagulation Factor VIII to Overcome the Immune ResponseR15HL135658 · NHLBI · WESTERN WASHINGTON UNIVERSITY · PI SPIEGEL, PAUL CLINTON · 2017 to 2024
$1.2M
NHLBI NIH HHS R15 HL135658NHLBI NIH HHS U54 HL141981
6 · The paper itself

Abstract

backgroundFollowing proteolytic activation, activated blood coagulation factor (F)VIII (FVIIIa) binds to activated platelet membranes, forming the intrinsic tenase complex with activated FIX (FIXa). Previous studies have identified the C1 and C2 domains as the membrane binding domains of FVIII through conserved arginine residues. A membrane binding model for the FVIII C domains proposes that surface-exposed hydrophobic and positively charged residues at each C domain interact with the membrane, yet a comprehensive thermodynamic and structural description of this interaction is lacking.

objectivesTo determine residues of interaction, thermodynamics, and membrane binding preference for FVIII membrane association.

methodsThe binding of FVIII constructs to lipid nanodiscs was characterized by nuclear magnetic resonance, isothermal titration calorimetry, bio-layer interferometry, and X-ray crystallography.

resultsThe thermodynamics of FVIII membrane binding indicated that the C1 domain associates through an enthalpically driven process while the C2 domain is entropically driven. Alanine mutations to surface-exposed hydrophobic residues in the C2 domain revealed differential effects on membrane binding, highlighting important determinants at the residue level. The structure of a C2 double mutant, L2251A/L2252A, demonstrated that its decreased affinity is likely due to decreasing the surface area hydrophobicity. Nuclear magnetic resonance studies with the C2 domain identified residues of interaction with soluble O-phospho-L-serine as well as lipid nanodiscs. Lastly, increasing phosphatidylethanolamine and decreasing phosphatidylserine content decreased overall FVIII affinity for membrane surfaces.

conclusionThis study provides further insight into the molecular basis for how FVIII interacts with platelets to form the intrinsic tenase complex.

Indexed as

Blood PlateletsFactor VIIINanostructuresPlatelet ActivationBinding SitesHumansHydrophobic and Hydrophilic InteractionsModels, MolecularMutationPhosphatidylserinesProtein BindingProtein DomainsThermodynamicsF8 protein, humanFactor VIIIPhosphatidylserinesblood coagulationfactor VIIIlipid membraneprotein/lipid interactionsthermodynamics

Identifiers

PMID39549835
PMCPMC11786986

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.