Evidence map›Paper›PMID 23754288›Full record

ArticleThe Journal of biological chemistry2013

Mapping the binding region on the low density lipoprotein receptor for blood coagulation factor VIII.

James H Kurasawa, Svetlana A Shestopal, Elena Karnaukhova, Evi B Struble, Timothy K Lee, Andrey G Sarafanov

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

6 citing papers in PubMed, 18 citations in OpenAlex.

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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 1 institution in 1 country.

James H KurasawaCenter for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA.
Svetlana A Shestopal
Elena Karnaukhova
Evi B Struble
Timothy K Lee
Andrey G Sarafanov
Center for Biologics Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Low density lipoprotein receptor (LDLR) was shown to mediate clearance of blood coagulation factor VIII (FVIII) from the circulation. To elucidate the mechanism of interaction of LDLR and FVIII, our objective was to identify the region of the receptor necessary for binding FVIII. Using surface plasmon resonance, we found that LDLR exodomain and its cluster of complement-type repeats (CRs) bind FVIII in the same mode. This indicated that the LDLR site for FVIII is located within the LDLR cluster. Similar results were obtained for another ligand of LDLR, α-2-macroglobulin receptor-associated protein (RAP), a common ligand of receptors from the LDLR family. We further generated a set of recombinant fragments of the LDLR cluster and assessed their structural integrity by binding to RAP and by circular dichroism. A number of fragments overlapping CR.2-5 of the cluster were positive for binding RAP and FVIII. The specificity of these interactions was tested by site-directed mutagenesis of conserved tryptophans within the LDLR fragments. For FVIII, the specificity was also tested using a single-chain variable antibody fragment directed against the FVIII light chain as a competitor. Both cases resulted in decreased binding, thus confirming its specificity. The mutagenic study also showed an importance of the conserved tryptophans in LDLR for both ligands, and the competitive binding results showed an involvement of the light chain of FVIII in its interaction with LDLR. In conclusion, the region of CR.2-5 of LDLR was defined as the binding site for FVIII and RAP.

Indexed as

Amino Acid SequenceBinding, CompetitiveBinding SitesCircular DichroismFactor VIIIHumansKineticsLDL-Receptor Related Protein-Associated ProteinMolecular Sequence DataMutagenesis, Site-DirectedMutationPeptide FragmentsProtein BindingProtein Interaction MappingReceptors, LDLRecombinant ProteinsFactor VIIILDL-Receptor Related Protein-Associated ProteinPeptide FragmentsReceptors, LDLRecombinant ProteinsBlood Coagulation FactorsFactor VIIIHemophilia ALipoprotein ReceptorReceptor Structure-FunctionRecombinant Protein Expression

Identifiers

PMID23754288
PMCPMC3724656
OpenAlexW2093683138

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.