Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.
Cholesterol Transport
Host–Pathogen Interaction
Leishmania
Phase-transition
Phospholipid Membranes
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
16
07
2024
accepted:
27
09
2024
revised:
23
09
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
aheadofprint
Résumé
The first step of successful infection by any intracellular pathogen relies on its ability to invade its host cell membrane. However, the detailed structural and molecular understanding underlying lipid membrane modification during pathogenic invasion remains unclear. In this study, we show that a specific Leishmania donovani (LD) protein, KMP-11, forms oligomers that bridge LD and host macrophage (MΦ) membranes. This KMP-11 induced interaction between LD and MΦ depends on the variations in cholesterol (CHOL) and ergosterol (ERG) contents in their respective membranes. These variations are crucial for the subsequent steps of invasion, including (a) the initial attachment, (b) CHOL transport from MΦ to LD, and (c) detachment of LD from the initial point of contact through a liquid ordered (Lo) to liquid disordered (Ld) membrane-phase transition. To validate the importance of KMP-11, we generate KMP-11 depleted LD, which failed to attach and invade host MΦ. Through tryptophan-scanning mutagenesis and synthesized peptides, we develop a generalized mathematical model, which demonstrates that the hydrophobic moment and the symmetry sequence code at the membrane interacting protein domain are key factors in facilitating the membrane phase transition and, consequently, the host cell infection process by Leishmania parasites.
Identifiants
pubmed: 39482488
doi: 10.1038/s44319-024-00302-7
pii: 10.1038/s44319-024-00302-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : DST | Science and Engineering Research Board (SERB)
ID : SRG/2020/000624/LS
Organisme : DST | Science and Engineering Research Board (SERB)
ID : PDF/2020/000678
Organisme : Indian Council of Medical Research (ICMR)
ID : 6/9-7(295)/2022-ECD-II
Organisme : CSIR | CSIR - Indian Institute of Chemical Biology (IICB)
ID : MLP136
Organisme : Indian National Science Academy (INSA)
ID : INSA/SP/SS/2024/253
Organisme : Indian Institute of Technology Kharagpur (IIT KGP)
ID : GATE
Organisme : CSIR/UGC
ID : NET/PMRF
Organisme : CSIR - Indian Institute of Chemical Biology (CSIR-IICB)
ID : HOPE
Organisme : Department of Biotechnology, Ministry of Science and Technology, India (DBT)
ID : BT/PR8475/BRB/10/1248/2013
Informations de copyright
© 2024. The Author(s).
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