Evidence map›Paper›PMID 27881302›Full record

ArticleCell2016

Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket.

Brandon Zimmerman, Brendan Kelly, Brian J McMillan, Tom C M Seegar, Ron O Dror, Andrew C Kruse, Stephen C Blacklow

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed
19.9field-weighted citation impact, top 1% 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

187 citing papers in PubMed, 293 citations in OpenAlex.

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  13. Frontiers in microbiology · 2026
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127 more citing papers are in PubMed but not listed here.

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 4 institutions in 1 country.

Brandon ZimmermanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
Brendan KellyDepartments of Computer Science and of Molecular and Cellular Physiology and Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA.
Brian J McMillanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
Tom C M SeegarDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
Ron O DrorDepartments of Computer Science and of Molecular and Cellular Physiology and Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA 94305, USA.
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: andrew_kruse@hms.harvard.edu.
Stephen C BlacklowDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: stephen_blacklow@hms.harvard.edu.
Dana-Farber Cancer Institute · USHarvard University · USStanford University · USBrigham and Women's Hospital · US

Funding

VASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7M
Structure and Function in Notch SignalingR01CA092433 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2002 to 2016
$5.0M
Molecular mechanisms of adiponectin signaling and PAQR functionDP5OD021345 · OD · HARVARD MEDICAL SCHOOL · PI KRUSE, ANDREW · 2015 to 2019
$2.1M
NCI NIH HHS R01 CA092433NHLBI NIH HHS T32 HL007627NIH HHS DP5 OD021345
6 · The paper itself

Abstract

Tetraspanins comprise a diverse family of four-pass transmembrane proteins that play critical roles in the immune, reproductive, genitourinary, and auditory systems. Despite their pervasive roles in human physiology, little is known about the structure of tetraspanins or the molecular mechanisms underlying their various functions. Here, we report the crystal structure of human CD81, a full-length tetraspanin. The transmembrane segments of CD81 pack as two largely separated pairs of helices, capped by the large extracellular loop (EC2) at the outer membrane leaflet. The two pairs of helices converge at the inner leaflet to create an intramembrane pocket with additional electron density corresponding to a bound cholesterol molecule within the cavity. Molecular dynamics simulations identify an additional conformation in which EC2 separates substantially from the transmembrane domain. Cholesterol binding appears to modulate CD81 activity in cells, suggesting a potential mechanism for regulation of tetraspanin function.

Indexed as

Molecular Dynamics SimulationBinding SitesCholesterolCrystallography, X-RayHumansModels, ChemicalTetraspanin 28CD81 protein, humanCholesterolTetraspanin 28CD19CD81membrane proteinprotein structureprotein traffickingX-ray crystallography

Identifiers

PMID27881302
PMCPMC5127602
OpenAlexW2543384879

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.