Evidence map›Paper›PMID 21454587›Full record

ArticleThe Journal of biological chemistry2011

Glycine dimerization motif in the N-terminal transmembrane domain of the high density lipoprotein receptor SR-BI required for normal receptor oligomerization and lipid transport.

Leonid Gaidukov, Andrew R Nager, Shangzhe Xu, Marsha Penman, Monty Krieger

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

41 citing papers in PubMed, 65 citations in OpenAlex.

  1. Design principles of the common Gly-X6-Gly membrane protein building block.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  5. Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  6. Article
  7. Review
  8. Inherited Variants inCirculation research · 2021
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  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
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  16. 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

5 authors at 1 institution in 1 country.

Leonid GaidukovDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Andrew R Nager
Shangzhe Xu
Marsha Penman
Monty Krieger
Massachusetts Institute of Technology · US

Funding

Platelets in Cardiovascular Biology and PathologyP01HL066105 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HYNES, RICHARD O · 2001 to 2010
$28.4M
SCAVENGER RECEPTORS--LIGAND BINDING AND PATHOPHYSIOLOGYR01HL052212 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KRIEGER, MONTY · 1994 to 2011
$5.4M
NHLBI NIH HHS HL066105NHLBI NIH HHS HL52212NHLBI NIH HHS P01 HL066105NHLBI NIH HHS R01 HL052212
6 · The paper itself

Abstract

Scavenger receptor class B, type I (SR-BI), a CD36 superfamily member, is an oligomeric high density lipoprotein (HDL) receptor that mediates negatively cooperative HDL binding and selective lipid uptake. We identified in the N-terminal transmembrane (N-TM) domain of SR-BI a conserved glycine dimerization motif, G(15)X(2)G(18)X(3)AX(2)G(25), of which the submotif G(18)X(3)AX(2)G(25) significantly contributes to homodimerization and lipid uptake activity. SR-BI variants were generated by mutations (single or multiple Gly → Leu substitutions) or by replacing the N-TM domain with those from other CD36 superfamily members containing (croquemort) or lacking (lysosomal integral membrane protein (LIMP) II) this glycine motif (chimeras). None of the SR-BI variants exhibited altered surface expression (based on antibody binding) or HDL binding. However, the G15L/G18L/G25L triple mutant exhibited reductions in cell surface homo-oligomerization (>10-fold) and the rate of selective lipid uptake (∼ 2-fold). Gly(18) and Gly(25) were necessary for normal lipid uptake activity of SR-BI and the SR-BI/croquemort chimera. The lipid uptake activity of the glycine motif-deficient SR-BI/LIMP II chimera was low but could be increased by introducing glycines at positions 18 and 25. The rate of lipid uptake mediated by SR-BI/LIMP II chimeras was proportional to the extent of receptor oligomerization. Thus, the glycine dimerization motif G(18)X(3)AX(2)G(25) in the N-TM domain of SR-BI contributes substantially to the homo-oligomerization and lipid transport activity of SR-BI but does not influence the negative cooperativity of HDL binding. Oligomerization-independent binding cooperativity suggests that classic allostery is not involved and that the negative cooperativity is probably the consequence of a "lattice effect" (interligand steric interference accompanying binding to adjacent receptors).

Indexed as

Amino Acid MotifsAmino Acid SubstitutionAnimalsBiological TransportChlorocebus aethiopsCHO CellsCOS CellsCricetinaeCricetulusHumansLipoproteins, HDLLysosomal Membrane ProteinsMiceMutation, MissenseProtein MultimerizationProtein Structure, TertiaryLipoproteins, HDLLysosomal Membrane ProteinsReceptors, ScavengerRecombinant Fusion ProteinsSCARB1 protein, humanScarb1 protein, mouseSCARB2 protein, humanScavenger Receptors, Class B

Identifiers

PMID21454587
PMCPMC3099662
OpenAlexW2064847654

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.