Evidence map›Paper›PMID 27402839›Full record

ArticleThe Journal of biological chemistry2016

High Affinity Binding of the Receptor-associated Protein D1D2 Domains with the Low Density Lipoprotein Receptor-related Protein (LRP1) Involves Bivalent Complex Formation: CRITICAL ROLES OF LYSINES 60 AND 191.

Joni M Prasad, Patricia A Young, Dudley K Strickland

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
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  5. A soluble derivative of PrPThe Journal of biological chemistry · 2020
    Article
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  8. Review
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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

3 authors at 1 institution in 1 country.

Joni M PrasadFrom the Center for Vascular and Inflammatory Disease and the Departments of Surgery and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Patricia A YoungFrom the Center for Vascular and Inflammatory Disease and the Departments of Surgery and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Dudley K StricklandFrom the Center for Vascular and Inflammatory Disease and the Departments of Surgery and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201 dstrickland@som.umaryland.edu.
University of Maryland, Baltimore · US

Funding

Role of Lipoprotein Receptors in Venous ThrombosisR01HL114379 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI STRICKLAND, DUDLEY K. · 2012 to 2016
$1.9M
Mechanisms by which LRP1 Protects the VasculatureR01HL120388 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI STRICKLAND, DUDLEY K. · 2014 to 2016
$1.1M
NHLBI NIH HHS R01 HL114379NHLBI NIH HHS R01 HL120388
6 · The paper itself

Abstract

The LDL receptor-related protein 1 (LRP1) is a large endocytic receptor that binds and mediates the endocytosis of numerous structurally diverse ligands. Currently, the basis for ligand recognition by LRP1 is not well understood. LRP1 requires a molecular chaperone, termed the receptor-associated protein (RAP), to escort the newly synthesized receptor from the endoplasmic reticulum to the Golgi. RAP is a three-domain protein that contains the following two high affinity binding sites for LRP1: one is located within domains 1 and 2, and one is located in its third domain. Studies on the interaction of the RAP third domain with LRP1 reveal critical contributions by lysine 256 and lysine 270 for this interaction. From these studies, a model for ligand recognition by this class of receptors has been proposed. Here, we employed surface plasmon resonance to investigate the binding of RAP D1D2 to LRP1. Our results reveal that the high affinity of D1D2 for LRP1 results from avidity effects mediated by the simultaneous interactions of lysine 60 in D1 and lysine 191 in D2 with sites on LRP1 to form a bivalent D1D2-LRP1 complex. When lysine 60 and 191 are both mutated to alanine, the binding of D1D2 to LRP1 is ablated. Our data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors, which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor.

Indexed as

Models, MolecularHumansLDL-Receptor Related Protein-Associated ProteinLow Density Lipoprotein Receptor-Related Protein-1LysineMultiprotein ComplexesProtein BindingProtein DomainsLDL-Receptor Related Protein-Associated ProteinLow Density Lipoprotein Receptor-Related Protein-1LRP1 protein, humanLysineMultiprotein Complexeschaperoneligandlow density lipoprotein (LDL)LRP1mutagenesisRAPreceptor endocytosissurface plasmon resonance (SPR)

Identifiers

PMID27402839
PMCPMC5000088
OpenAlexW2509049369

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.