Evidence map›Paper›PMID 28264929›Full record

ArticleThe Journal of biological chemistry2017

The agouti-related peptide binds heparan sulfate through segments critical for its orexigenic effects.

Rafael Palomino, Hsiau-Wei Lee, Glenn L Millhauser

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Syndecans modulate ghrelin receptor signaling.Journal of molecular endocrinology · 2025
    Article
  2. Review
  3. Article
  4. Genetic Deletion ofNutrients · 2019
    Article
  5. Review
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.

Rafael PalominoFrom the Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064.
Hsiau-Wei LeeFrom the Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064.
Glenn L MillhauserFrom the Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064 glennm@ucsc.edu.

Funding

UNIVERSITY OF CALIFORNIA, SANTA CRUZ IMSD PROGRAMR25GM058903 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI JURICA, MELISSA S · 1999 to 2019
$12.2M
Molecular Determinants of AGRP FunctionR01DK064265 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI MILLHAUSER, GLENN L · 2003 to 2013
$3.0M
800 MHz NMR Spectrometer and Helium CryoprobeS10OD018455 · OD · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI MILLHAUSER, GLENN L · 2015 to 2015
$2.0M
Molecular Mechanisms of AgRP SignalingR01DK110403 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI MILLHAUSER, GLENN L · 2017 to 2020
$1.7M
The Role of Syndecans in Melanocortin Signaling and Energy BalanceF31DK102343 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI PALOMINO, RAFAEL · 2014 to 2016
$94k
NIDDK NIH HHS F31 DK102343NIDDK NIH HHS R01 DK064265NIDDK NIH HHS R01 DK110403NIGMS NIH HHS R25 GM058903NIH HHS S10 OD018455
6 · The paper itself

Abstract

Syndecans potently modulate agouti-related peptide (AgRP) signaling in the central melanocortin system. Through heparan sulfate moieties, syndecans are thought to anchor AgRP near its receptor, enhancing its orexigenic effects. Original work proposed that the N-terminal domain of AgRP facilitates this interaction. However, this is not compatible with evidence that this domain is posttranslationally cleaved. Addressing this long-standing incongruity, we used calorimetry and magnetic resonance to probe interactions of AgRP peptides with glycosaminoglycans, including heparan sulfate. We show that mature, cleaved, C-terminal AgRP, not the N-terminal domain, binds heparan sulfate. NMR shows that the binding site consists of regions distinct from the melanocortin receptor-binding site. Using a library of designed AgRP variants, we find that the strength of the syndecan interaction perfectly tracks orexigenic action. Our data provide compelling evidence that AgRP is a heparan sulfate-binding protein and localizes critical regions in the AgRP structure required for this interaction.

Indexed as

Agouti-Related ProteinHeparan SulfateHumansPeptidesProtein BindingProtein DomainsAgouti-Related ProteinAGRP protein, humanHeparan SulfatePeptidesAgRPglycosaminoglycanG protein-coupled receptor (GPCR)heparan sulfateheparin-binding proteinmc4rneuropeptidesyndecan

Identifiers

PMID28264929
PMCPMC5418061

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.