Evidence map›Paper›PMID 22275220›Full record

ArticleScience signaling2012

A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria.

Christine L Gee, Kadamba G Papavinasasundaram, Sloane R Blair, Christina E Baer, Arnold M Falick, David S King, Jennifer E Griffin, Harene Venghatakrishnan, Andrew Zukauskas, Jun-Rong Wei and 5 more

Abstract read
In one paragraph

Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
13.0field-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

104 citing papers in PubMed, 177 citations in OpenAlex.

  1. Article
  2. Article
  3. An activator of a two-component system controls cell separation and intrinsic drug resistance inProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
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  11. Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
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  20. Article

44 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

15 authors at 2 institutions in 1 country.

Christine L GeeDepartment of Molecular and Cell Biology, QB3 Institute, University of California, Berkeley, Berkeley, CA 94720-3220, USA.
Kadamba G Papavinasasundaram
Sloane R Blair
Christina E Baer
Arnold M Falick
David S King
Jennifer E Griffin
Harene Venghatakrishnan
Andrew Zukauskas
Jun-Rong Wei
Rakesh K Dhiman
Dean C Crick
Eric J Rubin
Christopher M Sassetti
Tom Alber
University of Massachusetts Chan Medical School · USHarvard University · US

Funding

The Cloning Protein Production, Crystallization, and X-ray Data Collection CoreP01AI068135 · NIAID · TEXAS A&M AGRILIFE RESEARCH · PI ALBER, THOMAS C · 2006 to 2010
$13.2M
Sterol/Hopanoid Biosynthesis: An Anti-TB Drug TargetR01AI049151 · NIAID · COLORADO STATE UNIVERSITY-FORT COLLINS · PI CRICK, DEAN C · 2001 to 2019
$4.1M
Tuberculosis Pathogenesis and Drug ResponseR01AI064282 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SASSETTI, CHRISTOPHER M · 2007 to 2017
$3.9M
Functions and Mechanisms of M. Tuberculosis S/T KinasesR01GM070962 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ALBER, THOMAS C · 2005 to 2012
$2.2M
Drug Targets for TuberculosisR01AI071881 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI RUBIN, ERIC J. · 2009 to 2010
$802k
Targets for short-course TB therapy R21AI073509 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SASSETTI, CHRISTOPHER M · 2007 to 2008
$442k
Menaquinone biosynthesis: a drug target in Gram-positive bacteriaR56AI049151 · NIAID · COLORADO STATE UNIVERSITY · PI CRICK, DEAN C · 2007 to 2007
$320k
Howard Hughes Medical InstituteNIAID NIH HHS AI049151NIAID NIH HHS AI064282NIAID NIH HHS AI071881NIAID NIH HHS AI073509NIAID NIH HHS AI68135NIAID NIH HHS P01 AI068135NIAID NIH HHS R01 AI049151NIAID NIH HHS R01 AI064282NIAID NIH HHS R01 AI071881NIAID NIH HHS R21 AI073509NIAID NIH HHS R56 AI049151NIGMS NIH HHS GM70962NIGMS NIH HHS R01 GM070962
6 · The paper itself

Abstract

Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-responsive Ser-Thr protein kinase (STPK), initiates complex assembly by phosphorylating a kinase-like domain in the essential PG biosynthetic protein, MviN. This domain was structurally diverged from active kinases and did not mediate phosphotransfer. Threonine phosphorylation of the pseudokinase domain recruited the FhaA protein through its forkhead-associated (FHA) domain. The crystal structure of this phosphorylated pseudokinase-FHA domain complex revealed the basis of FHA domain recognition, which included unexpected contacts distal to the phosphorylated threonine. Conditional degradation of these proteins in mycobacteria demonstrated that MviN was essential for growth and PG biosynthesis and that FhaA regulated these processes at the cell poles and septum. Controlling this spatially localized PG regulatory complex is only one of several cellular roles ascribed to PknB, suggesting that the capacity to coordinate signaling across multiple processes is an important feature conserved between eukaryotic and prokaryotic STPK networks.

Indexed as

Cell WallMycobacterium tuberculosisPeptidoglycanPhosphorylationProtein Serine-Threonine KinasesSignal TransductionThreoninePeptidoglycanPknB protein, Mycobacterium tuberculosisProtein Serine-Threonine KinasesThreonine

Identifiers

PMID22275220
PMCPMC3664666
OpenAlexW2099929909

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.