Evidence map›Paper›PMID 27102061›Full record

ArticleScientific reports2016

Structural basis for the specific inhibition of glycoprotein Ibα shedding by an inhibitory antibody.

Yue Tao, Xiaoqin Zhang, Xin Liang, Jianye Zang, Xi Mo, Renhao Li

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Effect of Pneumatic Tubing System Transport on Platelet Apheresis Units.Cardiovascular engineering and technology · 2018
    Article
  7. Review
  8. Article
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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

6 authors at 5 institutions in 2 countries.

Yue TaoKey Laboratory of Pediatric Hematology &Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoqin ZhangKey Laboratory of Pediatric Hematology &Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xin LiangAflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Jianye ZangHefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences; University of Science and Technology of China, Hefei, China.
Xi MoKey Laboratory of Pediatric Hematology &Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Renhao LiAflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Shanghai Children's Medical Center · CNCenter for Cancer and Blood Disorders · USEmory University · USMicroscale (United States) · USShanghai Jiao Tong University · CN

Funding

Structure and Function of Platelet Glycoprotein lb-IX-V ComplexR01HL082808 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, RENHAO · 2006 to 2023
$6.4M
GPIbalpha shedding and platelet clearanceR01HL123984 · NHLBI · EMORY UNIVERSITY · PI LI, RENHAO · 2015 to 2018
$1.6M
NHLBI NIH HHS R01 HL082808NHLBI NIH HHS R01 HL123984
6 · The paper itself

Abstract

Ectodomain shedding of glycoprotein (GP) Ibα is thought to mediate the clearance of activated, aged or damaged platelets. A monoclonal antibody, 5G6, has been developed recently to specifically bind to the GPIbα shedding cleavage site and to inhibit its shedding. However, the molecular mechanism underlying antigen recognition and inhibitory specificity is not clear. To elucidate the structural basis for 5G6 binding to GPIbα, we determined the crystal structure of 5G6 Fab fragment in complex with its epitope peptide KL10 (GPIbα residues 461-470, KLRGVLQGHL), to 2.4-Å resolution. Key residues in both 5G6 and KL10 were mutated to validate their effects in antibody binding by using isothermal titration calorimetry. The 5G6 Fab-KL10 peptide complex structure confirmed the direct association of 5G6 with its target GPIbα residues and elucidated the molecular basis underlying its binding specificity and high affinity. The similar binding properties of 5G6 Fab fragment to GPIbα on human platelets as those to KL10 suggests that such an interaction may not be affected by the plasma membrane or nearby GPIbβ. This structural information may facilitate further antibody optimization and humanization.

Indexed as

Antibodies, MonoclonalBlood PlateletsCalorimetryCrystallography, X-RayDNA Mutational AnalysisHumansPlatelet Glycoprotein GPIb-IX ComplexProtein BindingAntibodies, MonoclonalPlatelet Glycoprotein GPIb-IX Complex

Identifiers

PMID27102061
PMCPMC4840364
OpenAlexW2336327202

What OpenQuestion holds

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LicenceCC BY
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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.