Evidence map›Paper›PMID 24863057›Full record

ArticleBiochimica et biophysica acta2014

Glutamate provides a key structural contact between reticulon-4 (Nogo-66) and phosphocholine.

Ali Alhoshani, Rosemarie Vithayathil, Jonathan Bandong, Katherine M Chrunyk, Gabriel O Moreno, Gregory A Weiss, Melanie J Cocco

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 95% 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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

7 authors at 1 institution in 1 country.

Ali AlhoshaniDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA.
Rosemarie VithayathilDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Jonathan BandongDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Katherine M ChrunykDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Gabriel O MorenoDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Gregory A WeissDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA; Department of Chemistry, University of California, Irvine, CA 92697, USA.
Melanie J CoccoDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA. Electronic address: mcocco@uci.edu.
University of California, Irvine · US

Funding

pH-Triggered Membrane Insertion of ProteinsR01GM069783 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COCCO, MELANIE J, KURNIKOVA, MARIA G · 2004 to 2014
$2.5M
Engineering Soluble Aggregation-Prone and Membrane-Bound ProteinsR01GM078528 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI WEISS, GREGORY A. · 2006 to 2010
$1.3M
Membrane Protein Co- Crystallization with Highly Crystalline and Soluble ProteinsR01GM100700 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI WEISS, GREGORY A. · 2012 to 2015
$1.1M
NIGMS NIH HHS GM069783NIGMS NIH HHS R01 GM069783NIGMS NIH HHS R01-GM069783-06NIGMS NIH HHS R01 GM078528NIGMS NIH HHS R01-GM078528-0NIGMS NIH HHS R01 GM100700NIGMS NIH HHS R01-GM100700-01
6 · The paper itself

Abstract

Human reticulon 4 (RTN-4) has been identified as the neurite outgrowth inhibitor (Nogo). This protein contains a span of 66 amino acids (Nogo-66) flanked by two membrane helices at the C-terminus. We previously determined the NMR structure of Nogo-66 in a native-like environment and defined the regions of Nogo-66 expected to be membrane embedded. We hypothesize that aromatic groups and a negative charge hyperconserved among RTNs (Glu26) drive the remarkably strong association of Nogo-66 with a phosphocholine surface. Glu26 is an isolated charge with no counterion provided by nearby protein groups. We modeled the docking of dodecylphosphocholine (DPC) with Nogo-66 and found that a lipid choline group could form a stable salt bridge with Glu26 and serve as a membrane anchor point. To test the role of the Glu26 anion in binding choline, we mutated this residue to alanine and assessed the structural consequences, the association with lipid and the affinity for the Nogo receptor. In an aqueous environment, Nogo-66 Glu26Ala is more helical than WT and binds the Nogo receptor with higher affinity. Thus, we can conclude that in the absence of a neutralizing positive charge provided by lipid, the glutamate anion is destabilizing to the Nogo-66 fold. Although the Nogo-66 Glu26Ala free energy of transfer from water into lipid is similar to that of WT, NMR data reveal a dramatic loss of tertiary structure for the mutant in DPC micelles. These data show that Glu26 has a key role in defining the structure of Nogo-66 on a phosphocholine surface. This article is part of a special issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

Indexed as

Amino Acid SequenceCircular DichroismGlutamic AcidHumansMagnetic Resonance SpectroscopyMembrane ProteinsMicellesMyelin ProteinsNogo ProteinsPeptidesPhosphorylcholineProtein BindingProtein ConformationProtein Structure, SecondarydodecylphosphocholineGlutamic AcidMembrane ProteinsMicellesMyelin ProteinsNogo ProteinsPeptidesPhosphorylcholineRTN4 protein, humanCholineGlutamateMembrane interfaceNogo-66ReticulonStructure

Identifiers

PMID24863057
PMCPMC4098973
OpenAlexW1969800355

What OpenQuestion holds

Textmetadata
LicenceTDM
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.