PMID- 35889137
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2076-2607 (Print)
IS  - 2076-2607 (Electronic)
IS  - 2076-2607 (Linking)
VI  - 10
IP  - 7
DP  - 2022 Jul 14
TI  - Plasmodium falciparum S-Adenosylmethionine Synthetase Is Essential for Parasite 
      Survival through a Complex Interaction Network with Cytoplasmic and Nuclear 
      Proteins.
LID - 10.3390/microorganisms10071419 [doi]
LID - 1419
AB  - S-adenosylmethionine synthetase (SAMS) is a key enzyme for the synthesis of the 
      lone methyl donor S-adenosyl methionine (SAM), which is involved in 
      transmethylation reactions and hence required for cellular processes such as DNA, 
      RNA, and histone methylation, but also polyamine biosynthesis and proteostasis. 
      In the human malaria parasite Plasmodium falciparum, PfSAMS is encoded by a 
      single gene and has been suggested to be crucial for malaria pathogenesis and 
      transmission; however, to date, PfSAMS has not been fully characterized. To gain 
      deeper insight into the function of PfSAMS, we generated a conditional gene 
      knockdown (KD) using the glmS ribozyme system. We show that PfSAMS localizes to 
      the cytoplasm and the nucleus of blood-stage parasites. PfSAMS-KD results in 
      reduced histone methylation and leads to impaired intraerythrocytic growth and 
      gametocyte development. To further determine the interaction network of PfSAMS, 
      we performed a proximity-dependent biotin identification analysis. We identified 
      a complex network of 1114 proteins involved in biological processes such as cell 
      cycle control and DNA replication, or transcription, but also in 
      phosphatidylcholine and polyamine biosynthesis and proteasome regulation. Our 
      findings highlight the diverse roles of PfSAMS during intraerythrocytic growth 
      and sexual stage development and emphasize that PfSAMS is a potential drug 
      target.
FAU - Musabyimana, Jean Pierre
AU  - Musabyimana JP
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Distler, Ute
AU  - Distler U
AUID- ORCID: 0000-0002-8031-6384
AD  - Proteomics Core Facility, Institute of Immunology, University Medical Center of 
      the Johannes-Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, 
      Germany.
FAU - Sassmannshausen, Juliane
AU  - Sassmannshausen J
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Berks, Christina
AU  - Berks C
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Manti, Janice
AU  - Manti J
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Bennink, Sandra
AU  - Bennink S
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Blaschke, Lea
AU  - Blaschke L
AUID- ORCID: 0000-0003-1006-2793
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Burda, Paul-Christian
AU  - Burda PC
AD  - Centre for Structural Systems Biology (CSSB) c/o DESY, Bernhard Nocht Institute, 
      University of Hamburg, Notkestrasse 85, Building 15, 22607 Hamburg, Germany.
FAU - Flammersfeld, Ansgar
AU  - Flammersfeld A
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Tenzer, Stefan
AU  - Tenzer S
AUID- ORCID: 0000-0003-3034-0017
AD  - Proteomics Core Facility, Institute of Immunology, University Medical Center of 
      the Johannes-Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, 
      Germany.
FAU - Ngwa, Che Julius
AU  - Ngwa CJ
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
FAU - Pradel, Gabriele
AU  - Pradel G
AUID- ORCID: 0000-0003-2264-5558
AD  - Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH 
      Aachen University, Worringerweg 1, 52074 Aachen, Germany.
LA  - eng
GR  - PR905/19-1 (SPP 2225); TE599/9-1 (SPP 2225); PR905/20-1; NG170/1-1/Deutsche 
      Forschungsgemeinschaft/
GR  - PhD Stipend JPM/Deutscher Akademischer Austauschdienst/
PT  - Journal Article
DEP - 20220714
PL  - Switzerland
TA  - Microorganisms
JT  - Microorganisms
JID - 101625893
PMC - PMC9320499
OTO - NOTNLM
OT  - Plasmodium falciparum
OT  - SAM
OT  - SAMS
OT  - drug target
OT  - histone methylation
OT  - interactome
OT  - malaria
OT  - polyamine biosynthesis
OT  - proteasome
OT  - transcriptional regulation
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/14
CRDT- 2022/07/27 01:33
PHST- 2022/05/31 00:00 [received]
PHST- 2022/07/01 00:00 [revised]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/07/27 01:33 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/14 00:00 [pmc-release]
AID - microorganisms10071419 [pii]
AID - microorganisms-10-01419 [pii]
AID - 10.3390/microorganisms10071419 [doi]
PST - epublish
SO  - Microorganisms. 2022 Jul 14;10(7):1419. doi: 10.3390/microorganisms10071419.