Evidence map›Paper›PMID 26346528›Full record

ArticleBiochemistry2015

Membrane Interaction of the Factor VIIIa Discoidin Domains in Atomistic Detail.

Jesper J Madsen, Y Zenmei Ohkubo, Günther H Peters, Johan H Faber, Emad Tajkhorshid, Ole H Olsen

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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

22 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  3. CaThe journal of physical chemistry. B · 2025
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  20. Lipid specificity of the membrane binding domain of coagulation factor X.Journal of thrombosis and haemostasis : JTH · 2017
    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

6 authors at 3 institutions in 2 countries.

Jesper J MadsenGlobal Research, Novo Nordisk A/S , DK-2760 Måløv, Denmark.
Y Zenmei Ohkubo
Günther H PetersDepartment of Chemistry, Technical University of Denmark , DK-2800 Kgs. Lyngby, Denmark.
Johan H FaberGlobal Research, Novo Nordisk A/S , DK-2760 Måløv, Denmark.
Emad Tajkhorshid
Ole H OlsenGlobal Research, Novo Nordisk A/S , DK-2760 Måløv, Denmark.
Novo Nordisk (Denmark) · DKTechnical University of Denmark · DKUniversity of Illinois Urbana-Champaign · US

Funding

Synthetic Antigen Binder CoreU54GM087519 · NIGMS · UNIVERSITY OF CHICAGO · PI ROUX, BENOIT · 2010 to 2017
$31.9M
WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI TAJKHORSHID, EMAD · 2012 to 2021
$19.0M
Understanding the role of phospholipids in integrin signalingR01GM101048 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SLIGAR, STEPHEN G. · 2012 to 2015
$1.1M
NIGMS NIH HHS P41 GM104601NIGMS NIH HHS P41-GM104601NIGMS NIH HHS R01 GM101048NIGMS NIH HHS R01-GM101048NIGMS NIH HHS U54 GM087519NIGMS NIH HHS U54-GM087519
6 · The paper itself

Abstract

A recently developed membrane-mimetic model was applied to study membrane interaction and binding of the two anchoring C2-like discoidin domains of human coagulation factor VIIIa (FVIIIa), the C1 and C2 domains. Both individual domains, FVIII C1 and FVIII C2, were observed to bind the phospholipid membrane by partial or full insertion of their extruding loops (the spikes). However, the two domains adopted different molecular orientations in their membrane-bound states; FVIII C2 roughly was positioned normal to the membrane plane, while FVIII C1 displayed a multitude of tilted orientations. The results indicate that FVIII C1 may be important in modulating the orientation of the FVIIIa molecule to optimize the interaction with FIXa, which is anchored to the membrane via its γ-carboxyglutamic acid-rich (Gla) domain. Additionally, a structural change was observed in FVIII C1 in the coiled main chain leading the first spike. A tight interaction with one lipid per domain, similar to what has been suggested for the homologous FVa C2, is characterized. Finally, we rationalize known FVIII antibody epitopes and the scarcity of documented hemophilic missense mutations related to improper membrane binding of FVIIIa, based on the prevalent nonspecificity of ionic interactions in the simulated membrane-bound states of FVIII C1 and FVIII C2.

Indexed as

Membranes, ArtificialEpitopesFactor VIIIHemophilia AHumansMutation, MissensePhospholipidsProtein Structure, SecondaryProtein Structure, TertiaryEpitopesF8 protein, humanFactor VIIIMembranes, ArtificialPhospholipids

Identifiers

PMID26346528
PMCPMC5050047
OpenAlexW1627916641

What OpenQuestion holds

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Registered trials

None linked

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.