Evidence map›Paper›PMID 19397492›Full record

ArticleThe Biochemical journal2009

Receptor-associated protein (RAP) has two high-affinity binding sites for the low-density lipoprotein receptor-related protein (LRP): consequences for the chaperone functions of RAP.

Jan K Jensen, Klavs Dolmer, Christine Schar, Peter G W Gettins

Open access · bronzeAbstract read
In one paragraph

Article in The Biochemical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 27% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 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

4 authors at 1 institution in 1 country.

Jan K JensenDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S. Ashland, M/C 669, Chicago, IL 60607, USA.
Klavs Dolmer
Christine Schar
Peter G W Gettins
University of Illinois Chicago · US

Funding

STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRPR01GM054414 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GETTINS, PETER G.W. · 1996 to 2014
$3.7M
Structural examination of serpin-protein interactionsR01HL079430 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GETTINS, PETER G.W. · 2005 to 2009
$1.9M
Protein interactions by analytical ultracentrifugationS10RR022361 · NCRR · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GETTINS, PETER G.W. · 2007 to 2007
$334k
NCRR NIH HHS S10 RR22361NHLBI NIH HHS HL79430NIGMS NIH HHS R01 GM54414
6 · The paper itself

Abstract

RAP (receptor-associated protein) is a three domain 38 kDa ER (endoplasmic reticulum)-resident protein that is a chaperone for the LRP (low-density lipoprotein receptor-related protein). Whereas RAP is known to compete for binding of all known LRP ligands, neither the location, the number of binding sites on LRP, nor the domains of RAP involved in binding is known with certainty. We have systematically examined the binding of each of the three RAP domains (D1, D2 and D3) to tandem and triple CRs (complement-like repeats) that span the principal ligand-binding region, cluster II, of LRP. We found that D3 binds with low nanomolar affinity to all (CR)2 species examined. Addition of a third CR domain increases the affinity for D3 slightly. A pH change from 7.4 to 5.5 gave only a 6-fold increase in Kd for D3 at 37 degrees C, whereas temperature change from 22 degrees C to 37 degrees C has a similar small effect on affinity, raising questions about the recently proposed D3-destabilization mechanism of RAP release from LRP. Surprisingly, and in contrast to literature suggestions, D1 and D2 also bind to most (CR)2 and (CR)3 constructs with nanomolar affinity. Although this suggested that there might be three high-affinity binding sites in RAP for LRP, studies with intact RAP showed that only two binding sites are available in the intact chaperone. These findings suggest a new model for RAP to function as a folding chaperone and also for the involvement of YWTD domains in RAP release from LRP in the Golgi.

Indexed as

Binding SitesHydrogen-Ion ConcentrationKineticsLDL-Receptor Related Protein-Associated ProteinLow Density Lipoprotein Receptor-Related Protein-1Models, MolecularMolecular ChaperonesProtein ConformationProtein FoldingProtein Structure, TertiarySpectrometry, FluorescenceTemperatureLDL-Receptor Related Protein-Associated ProteinLow Density Lipoprotein Receptor-Related Protein-1Molecular Chaperones

Identifiers

PMID19397492
PMCPMC2708935
OpenAlexW2075508995

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.