Evidence map›Paper›PMID 22078563›Full record

ArticleStructure (London, England : 1993)2011

Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein.

Valeria R Samygina, Alexander N Popov, Aintzane Cabo-Bilbao, Borja Ochoa-Lizarralde, Felipe Goni-de-Cerio, Xiuhong Zhai, Julian G Molotkovsky, Dinshaw J Patel, Rhoderick E Brown, Lucy Malinina

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Sphingolipids and their metabolism in physiology and disease.Nature reviews. Molecular cell biology · 2018
    Review
  12. Article
  13. Review
  14. Article
  15. Sphingolipid transfer proteins defined by the GLTP-fold.Quarterly reviews of biophysics · 2015
    Article
  16. Article
  17. Article
  18. Article
  19. Structural insights into lipid-dependent reversible dimerization of human GLTP.Acta crystallographica. Section D, Biological crystallography · 2013
    Article
  20. Article
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

10 authors at 5 institutions in 4 countries.

Valeria R SamyginaStructural Biology Unit, CIC bioGUNE, Technology Park of Bizkaia, 48160 Derio-Bilbao, Spain.
Alexander N Popov
Aintzane Cabo-Bilbao
Borja Ochoa-Lizarralde
Felipe Goni-de-Cerio
Xiuhong Zhai
Julian G Molotkovsky
Dinshaw J Patel
Rhoderick E Brown
Lucy Malinina
CIC bioGUNE · ESUniversity of Minnesota · USEuropean Synchrotron Radiation Facility · FRMemorial Sloan Kettering Cancer Center · USRussian Academy of Sciences · RU

Funding

GLYCOLIPID TRANSFER--REGULATION BY MEMBRANE INTERFACESR01GM045928 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BROWN, RHODERICK E · 1992 to 2014
$4.8M
MOLECULAR BASIS OF GLYCOSPHINGOLIPID BINDING SPECIFICITYR01CA121493 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI PATEL, DINSHAW J · 2006 to 2010
$1.2M
NCI NIH HHS CA121493NCI NIH HHS R01 CA121493NIGMS NIH HHS GM45928NIGMS NIH HHS R01 GM045928
6 · The paper itself

Abstract

Human glycolipid transfer protein (GLTP) fold represents a novel structural motif for lipid binding/transfer and reversible membrane translocation. GLTPs transfer glycosphingolipids (GSLs) that are key regulators of cell growth, division, surface adhesion, and neurodevelopment. Herein, we report structure-guided engineering of the lipid binding features of GLTP. New crystal structures of wild-type GLTP and two mutants (D48V and A47D‖D48V), each containing bound N-nervonoyl-sulfatide, reveal the molecular basis for selective anchoring of sulfatide (3-O-sulfo-galactosylceramide) by D48V-GLTP. Directed point mutations of "portal entrance" residues, A47 and D48, reversibly regulate sphingosine access to the hydrophobic pocket via a mechanism that could involve homodimerization. "Door-opening" conformational changes by phenylalanines within the hydrophobic pocket are revealed during lipid encapsulation by new crystal structures of bona fide apo-GLTP and GLTP complexed with N-oleoyl-glucosylceramide. The development of "engineered GLTPs" with enhanced specificity for select GSLs provides a potential new therapeutic approach for targeting GSL-mediated pathologies.

Indexed as

Amino Acid SubstitutionBinding SitesCarrier ProteinsCrystallography, X-RayHumansHydrogen BondingHydrophobic and Hydrophilic InteractionsModels, MolecularProtein BindingProtein MultimerizationSubstrate SpecificitySulfoglycosphingolipidsSurface PropertiesCarrier ProteinsGLTP protein, humanSulfoglycosphingolipids

Identifiers

PMID22078563
PMCPMC3220887
OpenAlexW2110334158

What OpenQuestion holds

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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.