PMID- 30183110
OWN - NLM
STAT- MEDLINE
DCOM- 20190828
LR  - 20240405
IS  - 1097-0134 (Electronic)
IS  - 0887-3585 (Print)
IS  - 0887-3585 (Linking)
VI  - 86
IP  - 11
DP  - 2018 Nov
TI  - Structural and biochemical characterization of Plasmodium falciparum Hsp70-x 
      reveals functional versatility of its C-terminal EEVN motif.
PG  - 1189-1201
LID - 10.1002/prot.25600 [doi]
AB  - Plasmodium falciparum, the main agent of malaria expresses six members of the 
      heat shock protein 70 (Hsp70) family. Hsp70s serve as protein folding 
      facilitators in the cell. Amongst the six Hsp70 species that P. falciparum 
      expresses, Hsp70-x (PfHsp70-x), is partially exported to the host red blood cell 
      where it is implicated in host cell remodeling. Nearly 500 proteins of parasitic 
      origin are exported to the parasite-infected red blood cell (RBC) along with 
      PfHsp70-x. The role of PfHsp70-x in the infected human RBC remains largely 
      unclear. One of the defining features of PfHsp70-x is the presence of EEVN 
      residues at its C-terminus. In this regard, PfHsp70-x resembles canonical 
      eukaryotic cytosol-localized Hsp70s which possess EEVD residues at their 
      C-termini in place of the EEVN residues associated with PfHsp70-x. The EEVD 
      residues of eukaryotic Hsp70s facilitate their interaction with co-chaperones. 
      Characterization of the role of the EEVN residues of PfHsp70-x could provide 
      insights into the function of this protein. In the current study, we expressed 
      and purified recombinant PfHsp70-x (full length) and its EEVN minus form 
      (PfHsp70-x(T) ). We then conducted structure- function assays towards 
      establishing the role of the EEVN motif of PfHsp70-x. Our findings suggest that 
      the EEVN residues of PfHsp70-x are important for its ATPase activity and 
      chaperone function. Furthermore, the EEVN residues are crucial for the direct 
      interaction between PfHsp70-x and human Hsp70-Hsp90 organizing protein (hHop) in 
      vitro. Hop facilitates functional cooperation between Hsp70 and Hsp90. However, 
      it remains to be established if PfHsp70-x and hHsp90 cooperate in vivo.
CI  - (c) 2018 The Authors. Proteins: Structure, Function, and Bioinformatics published 
      by Wiley Periodicals, Inc.
FAU - Mabate, Blessing
AU  - Mabate B
AD  - Department of Biochemistry, University of Venda, South Africa.
FAU - Zininga, Tawanda
AU  - Zininga T
AD  - Department of Biochemistry, University of Venda, South Africa.
FAU - Ramatsui, Lebogang
AU  - Ramatsui L
AD  - Department of Biochemistry, University of Venda, South Africa.
FAU - Makumire, Stanley
AU  - Makumire S
AD  - Department of Biochemistry, University of Venda, South Africa.
FAU - Achilonu, Ikechukwu
AU  - Achilonu I
AD  - Protein Structure-Function Research Unit, School of Molecular & Cell Biology, 
      University of the Witwatersrand, Johannesburg, South Africa.
FAU - Dirr, Heini W
AU  - Dirr HW
AD  - Protein Structure-Function Research Unit, School of Molecular & Cell Biology, 
      University of the Witwatersrand, Johannesburg, South Africa.
FAU - Shonhai, Addmore
AU  - Shonhai A
AUID- ORCID: 0000-0003-3203-0602
LA  - eng
GR  - 64788 7546492598/National Research Foundation of South Africa/International
GR  - Alexander von Humboldt-Stiftung/International
GR  - Claude Leon Foundation/International
GR  - L1/402/14-1/Deutsche Forschungsgemeinschaft/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180929
PL  - United States
TA  - Proteins
JT  - Proteins
JID - 8700181
RN  - 0 (HOPX protein, human)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
SB  - IM
MH  - Adenosine Triphosphatases/chemistry/metabolism
MH  - Amino Acid Motifs
MH  - HSP70 Heat-Shock Proteins/*chemistry/metabolism
MH  - Homeodomain Proteins/metabolism
MH  - Humans
MH  - Malaria, Falciparum/metabolism/*parasitology
MH  - Plasmodium falciparum/*chemistry/metabolism
MH  - Protein Binding
MH  - Protein Folding
MH  - Protein Interaction Maps
MH  - Protozoan Proteins/*chemistry/metabolism
MH  - Tumor Suppressor Proteins/metabolism
PMC - PMC6282620
OTO - NOTNLM
OT  - EEVN
OT  - PfHsp70-x
OT  - asparagine repeat rich peptide
OT  - chaperone
OT  - heat shock proteins
OT  - human hop
EDAT- 2018/09/06 06:00
MHDA- 2019/08/29 06:00
PMCR- 2018/12/06
CRDT- 2018/09/06 06:00
PHST- 2018/04/11 00:00 [received]
PHST- 2018/08/27 00:00 [revised]
PHST- 2018/08/31 00:00 [accepted]
PHST- 2018/09/06 06:00 [pubmed]
PHST- 2019/08/29 06:00 [medline]
PHST- 2018/09/06 06:00 [entrez]
PHST- 2018/12/06 00:00 [pmc-release]
AID - PROT25600 [pii]
AID - 10.1002/prot.25600 [doi]
PST - ppublish
SO  - Proteins. 2018 Nov;86(11):1189-1201. doi: 10.1002/prot.25600. Epub 2018 Sep 29.