Asset Details

MbrlCatalogueTitleDetail

Do you wish to reserve the book?

HaloPROTAC3 does not trigger the degradation of the halotagged parasitophorous vacuole membrane protein UIS4 during Plasmodium liver stage development

by Kumar, Jyothsna R. , Manneville, Carole , Mitchell, Gabriel , Fishbaugher, Matthew E. , Thiel, Zacharias , Saldivia, Manuel , Probst, Alexandra , Torres, Allison , Vaughan, Ashley M. , Marcellin, David , Hegde, Shreeya , Joyner, Chester J. , Torres, Laura , Lantigua, Ashley A. , Jennison, Charlie , Nyfeler, Beat , Aleshnick, Maya , Harupa, Anke , Lam, Melanie , Wilder, Brandon K. , Roberson, Sarah G. H. , Flannery, Erika L. , Mikolajczak, Sebastian A.

in 631/154 / 631/326/417 / 631/326/421 / 631/326/88 / 631/92/613 / 692/699/255/1629 / Animals / Biodegradation / Blood parasites / Chimeras / Cytosol / Degradation / Developmental stages / Hepatocytes / Hepatocytes - metabolism / Hepatocytes - parasitology / Humanities and Social Sciences / Humans / Hypnozoite / Induced proximity / Infectious disease / Liver / Liver - metabolism / Liver - parasitology / Malaria / Malaria - metabolism / Malaria - parasitology / Membrane Proteins - metabolism / Mice / Molecules / multidisciplinary / Parasites / Parasitophorous vacuole / Pathogens / Plasmodium / Plasmodium - growth & development / Plasmodium - metabolism / Plasmodium berghei - growth & development / Plasmodium berghei - metabolism / Proteins / Proteolysis / Protozoan Proteins - genetics / Protozoan Proteins - metabolism / Schizont / Science / Science (multidisciplinary) / Targeted protein degradation / Ubiquitin-protein ligase / Ubiquitination / Vacuoles - metabolism / Vacuoles - parasitology / Vector-borne diseases

2025

Yes Please

Hey, we have placed the reservation for you!

By the way, why not check out events that you can attend while you pick your title.

Oops! Something went wrong.

Looks like we were not able to place the reservation. Kindly try again later.

Are you sure you want to remove the book from the shelf?

HaloPROTAC3 does not trigger the degradation of the halotagged parasitophorous vacuole membrane protein UIS4 during Plasmodium liver stage development

2025

Confirm

Do you wish to request the book?

HaloPROTAC3 does not trigger the degradation of the halotagged parasitophorous vacuole membrane protein UIS4 during Plasmodium liver stage development

2025

Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy

How would you like to get it?

Submit

We have requested the book for you!

Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.

Oops! Something went wrong.

Looks like we were not able to place your request. Kindly try again later.

Journal Article

HaloPROTAC3 does not trigger the degradation of the halotagged parasitophorous vacuole membrane protein UIS4 during Plasmodium liver stage development

Kumar, Jyothsna R.,

Manneville, Carole,

Mitchell, Gabriel,

Fishbaugher, Matthew E.,

Thiel, Zacharias,

Saldivia, Manuel,

Probst, Alexandra,

Torres, Allison,

Vaughan, Ashley M.,

Marcellin, David,

Hegde, Shreeya,

Joyner, Chester J.,

Torres, Laura,

Lantigua, Ashley A.,

Jennison, Charlie,

Nyfeler, Beat,

Aleshnick, Maya,

Harupa, Anke,

Lam, Melanie,

Wilder, Brandon K.,

Roberson, Sarah G. H.,

Flannery, Erika L.,

Mikolajczak, Sebastian A.

2025

Overview

Targeted protein degradation (TPD) is a novel strategy for developing therapeutics against pathogens. Prior to causing malaria, Plasmodium parasites replicate within hepatocytes as liver stages, surrounded by a parasitophorous vacuole membrane (PVM). We hypothesized that TPD can be employed to trigger host-driven degradation of essential liver stage PVM proteins and lead to parasite death. To explore this, we took advantage of the proteolysis-targeting-chimera HaloPROTAC3, a molecule that recruits the host von Hippel-Lindau (VHL) E3 ligase to the HaloTag (HT). Parasites expressing HT fused to the host cytosol-exposed domain of the PVM protein UIS4 (UIS4-HT) were generated in Plasmodium berghei and Plasmodium cynomolgi , but only P. berghei UIS4-HT enabled productive liver stage infection experiments in vitro. Although HaloPROTAC3 triggered the degradation of HT proteins in host cells, it had no impact on the survival of P. berghei UIS4-HT liver stages. Furthermore, HaloPROTAC3 bound to P. berghei UIS4-HT but did not recruit VHL or trigger ubiquitination of the PVM. Overall, although this study did not establish whether host-driven TPD can degrade Plasmodium PVM proteins, it highlights the challenges of developing TPD approaches against novel targets and offers insights for advancing this therapeutic strategy against pathogens.

Share this book

Add to My Shelf

Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ Animals