Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology

Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability

Sabrina Pospich, Esa-Pekka Kumpula, Julian von der Ecken, Juha Vahokoski, Inari Kursula, and Stefan Raunser
PNAS October 3, 2017 114 (40) 10636-10641; published ahead of print September 18, 2017 https://doi.org/10.1073/pnas.1707506114
Sabrina Pospich
aDepartment of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sabrina Pospich
Esa-Pekka Kumpula
bBiocenter Oulu, University of Oulu, 90220 Oulu, Finland;cFaculty of Biochemistry and Molecular Medicine, University of Oulu, 90220 Oulu, Finland;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julian von der Ecken
aDepartment of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juha Vahokoski
bBiocenter Oulu, University of Oulu, 90220 Oulu, Finland;cFaculty of Biochemistry and Molecular Medicine, University of Oulu, 90220 Oulu, Finland;dDepartment of Biomedicine, University of Bergen, 5009 Bergen, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Inari Kursula
bBiocenter Oulu, University of Oulu, 90220 Oulu, Finland;cFaculty of Biochemistry and Molecular Medicine, University of Oulu, 90220 Oulu, Finland;dDepartment of Biomedicine, University of Bergen, 5009 Bergen, Norway
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Inari Kursula
  • For correspondence: inari.kursula@uib.nostefan.raunser@mpi-dortmund.mpg.de
Stefan Raunser
aDepartment of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stefan Raunser
  • For correspondence: inari.kursula@uib.nostefan.raunser@mpi-dortmund.mpg.de
  1. Edited by Thomas D. Pollard, Yale University, New Haven, CT, and approved August 21, 2017 (received for review May 5, 2017)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

The malaria parasite Plasmodium falciparum actively invades host cells, using a mechanism that relies on the interaction of the motor protein myosin and actin filaments which serve as tracks. We determined the structure of stabilized P. falciparum actin 1 filaments at near-atomic resolution using single-particle electron cryomicroscopy. The high resolution of the structure allowed us to identify important positions in the filament that are essential for the temporal and spatial control of actin polymerization and play a pivotal role in host cell invasion, and thus infectivity. In general, our study provides important insights into the structural design of actin filaments.

Abstract

During their life cycle, apicomplexan parasites, such as the malaria parasite Plasmodium falciparum, use actomyosin-driven gliding motility to move and invade host cells. For this process, actin filament length and stability are temporally and spatially controlled. In contrast to canonical actin, P. falciparum actin 1 (PfAct1) does not readily polymerize into long, stable filaments. The structural basis of filament instability, which plays a pivotal role in host cell invasion, and thus infectivity, is poorly understood, largely because high-resolution structures of PfAct1 filaments were missing. Here, we report the near-atomic structure of jasplakinolide (JAS)-stabilized PfAct1 filaments determined by electron cryomicroscopy. The general filament architecture is similar to that of mammalian F-actin. The high resolution of the structure allowed us to identify small but important differences at inter- and intrastrand contact sites, explaining the inherent instability of apicomplexan actin filaments. JAS binds at regular intervals inside the filament to three adjacent actin subunits, reinforcing filament stability by hydrophobic interactions. Our study reveals the high-resolution structure of a small molecule bound to F-actin, highlighting the potential of electron cryomicroscopy for structure-based drug design. Furthermore, our work serves as a strong foundation for understanding the structural design and evolution of actin filaments and their function in motility and host cell invasion of apicomplexan parasites.

  • F-actin
  • Plasmodium
  • cryo-EM
  • jasplakinolide
  • malaria

Footnotes

  • ↵1To whom correspondence may be addressed. Email: inari.kursula{at}uib.no or stefan.raunser{at}mpi-dortmund.mpg.de.
  • Author contributions: I.K. and S.R. designed research; S.P., E.-P.K., J.v.d.E., and J.V. performed research; S.P. analyzed data; and S.P., I.K., and S.R. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The electron density map after postprocessing has been deposited in the Electron Microscopy Data Bank (EMDB accession code 3805). The final model containing five actin subunits and three jasplakinolide molecules was submitted to the Protein Data Bank, www.pdb.org (PDB ID code 5OGW).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1707506114/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
Citation Tools
Malaria parasite F-actin structure
Sabrina Pospich, Esa-Pekka Kumpula, Julian von der Ecken, Juha Vahokoski, Inari Kursula, Stefan Raunser
Proceedings of the National Academy of Sciences Oct 2017, 114 (40) 10636-10641; DOI: 10.1073/pnas.1707506114

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Malaria parasite F-actin structure
Sabrina Pospich, Esa-Pekka Kumpula, Julian von der Ecken, Juha Vahokoski, Inari Kursula, Stefan Raunser
Proceedings of the National Academy of Sciences Oct 2017, 114 (40) 10636-10641; DOI: 10.1073/pnas.1707506114
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 116 (7)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results and Discussion
    • Concluding Remarks
    • Materials and Methods
    • SI Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Opinion: “Plan S” falls short for society publishers—and for the researchers they serve
Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Image credit: Dave Cutler (artist).
Several large or long-lived animals seem strangely resistant to developing cancer. Elucidating the reasons why could lead to promising cancer-fighting strategies in humans.
Core Concept: Solving Peto’s Paradox to better understand cancer
Several large or long-lived animals seem strangely resistant to developing cancer. Elucidating the reasons why could lead to promising cancer-fighting strategies in humans.
Image credit: Shutterstock.com/ronnybas frimages.
Featured Profile
PNAS Profile of NAS member and biochemist Hao Wu
 Nonmonogamous strawberry poison frog (Oophaga pumilio).  Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Putative signature of monogamy
A study suggests a putative gene-expression hallmark common to monogamous male vertebrates of some species, namely cichlid fishes, dendrobatid frogs, passeroid songbirds, common voles, and deer mice, and identifies 24 candidate genes potentially associated with monogamy.
Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Active lifestyles. Image courtesy of Pixabay/MabelAmber.
Meaningful life tied to healthy aging
Physical and social well-being in old age are linked to self-assessments of life worth, and a spectrum of behavioral, economic, health, and social variables may influence whether aging individuals believe they are leading meaningful lives.
Image courtesy of Pixabay/MabelAmber.

More Articles of This Classification

Biological Sciences

  • Structural basis for activity of TRIC counter-ion channels in calcium release
  • PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin
  • Altered neural odometry in the vertical dimension
Show more

Biophysics and Computational Biology

  • Structural basis for activity of TRIC counter-ion channels in calcium release
  • Five computational developability guidelines for therapeutic antibody profiling
  • Atomic-level characterization of protein–protein association
Show more

Related Content

  • No related articles found.
  • Scopus
  • PubMed
  • Google Scholar

Cited by...

  • High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing
  • Scopus (6)
  • Google Scholar

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Classics
  • Front Matter
  • Teaching Resources
  • Anthropology
  • Chemistry
  • Physics
  • Sustainability Science

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Press
  • Site Map

Feedback    Privacy/Legal

Copyright © 2019 National Academy of Sciences. Online ISSN 1091-6490