Summary: PFEMP DBL domain
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PfEMP1 (Plasmodium falciparum erythrocyte membrane protein) has been identified as the rosetting ligand of the malaria parasite P. falciparum [1,2]. Rosetting is the adhesion of infected erythrocytes with uninfected erythrocytes in the vasculature of the infected organ, and is associated with severe malaria. PfEMP1 interacts with Complement Receptor One on uninfected erythrocytes to form rosettes . The extreme variation within these proteins and the grouping of var genes implies that var gene recombination preferentially occurs within var gene groups. These groups reflect a functional diversification that has evolved to cope with the varying conditions of transmission and host immune response met by the parasite . A recombination hotspot was uncovered between Duffy-binding-like (DBL) subdomains . Solution of the crystal structure of the N-terminal and first DBL region of PfEMP1 from the VarO variant of the PfEMP1 protein is found to be directly implicated in rosetting as the heparin-binding site .
Chen Q, Barragan A, Fernandez V, Sundstrom A, Schlichtherle M, Sahlen A, Carlson J, Datta S, Wahlgren M; , J Exp Med 1998;187:15-23.: Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum. PUBMED:9419207 EPMC:9419207
Rowe JA, Moulds JM, Newbold CI, Miller LH; , Nature 1997;388:292-295.: P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. PUBMED:9230440 EPMC:9230440
Lavstsen T, Salanti A, Jensen AT, Arnot DE, Theander TG;, Malar J. 2003;2:27.: Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions. PUBMED:14565852 EPMC:14565852
Rask TS, Hansen DA, Theander TG, Gorm Pedersen A, Lavstsen T;, PLoS Comput Biol. 2010; [Epub ahead of print]: Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes--divide and conquer. PUBMED:20862303 EPMC:20862303
Juillerat A, Lewit-Bentley A, Guillotte M, Gangnard S, Hessel A, Baron B, Vigan-Womas I, England P, Mercereau-Puijalon O, Bentley GA;, Proc Natl Acad Sci U S A. 2011;108:5243-5248.: Structure of a Plasmodium falciparum PfEMP1 rosetting domain reveals a role for the N-terminal segment in heparin-mediated rosette inhibition. PUBMED:21402930 EPMC:21402930
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004258
PfEMP1 (Plasmodium falciparum erythrocyte membrane protein) has been identified as the rosetting ligand of the malaria parasite P. falciparum [PUBMED:9419207, PUBMED:9230440]. Rosetting is the adhesion of infected erythrocytes with uninfected erythrocytes in the vasculature of the infected organ, and is associated with severe malaria. PfEMP1 interacts with Complement Receptor One on uninfected erythrocytes to form rosettes [PUBMED:9230440]. The extreme variation within these proteins and the grouping of var genes implies that var gene recombination preferentially occurs within var gene groups. These groups reflect a functional diversification that has evolved to cope with the varying conditions of transmission and host immune response met by the parasite [PUBMED:14565852]. A recombination hotspot was uncovered between Duffy-binding-like (DBL) subdomains [PUBMED:20862303]. Solution of the crystal structure of the N-terminal and first DBL region of PfEMP1 from the VarO variant of the PfEMP1 protein is found to be directly implicated in rosetting as the heparin-binding site [PUBMED:21402930].
Malaria is still a major cause of mortality in many areas of the world. Plasmodium falciparum causes the most severe human form of the disease and is responsible for most fatalities. Severe cases of malaria can occur when the parasite invades and then proliferates within red blood cell erythrocytes. The parasite produces many variant antigenic proteins, encoded by multigene families, which are present on the surface of the infected erythrocyte and play important roles in virulence. A crucial survival mechanism for the malaria parasite is its ability to evade the immune response by switching these variant surface antigens. The high virulence of P. falciparum relative to other malarial parasites is in large part due to the fact that in this organism many of these surface antigens mediate the binding of infected erythrocytes to the vascular endothelium (cytoadherence) and non-infected erythrocytes (rosetting). This can lead to the accumulation of infected cells in the vasculature of a variety of organs, blocking the blood flow and reducing the oxygen supply. Clinical symptoms of severe infection can include fever, progressive anaemia, multi-organ dysfunction and coma. For more information see [PUBMED:10885986].
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We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Pfam-B_822 (release 6.4)|
|Author:||Griffiths-Jones SR, Bateman A|
|Number in seed:||11|
|Number in full:||2271|
|Average length of the domain:||135.30 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||14.59 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PFEMP domain has been found. There are 9 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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