Isolation and characterisation of genomic and cDNA clones coding for a serine-, alanine-, and proline-rich protein of Trypanosoma cruzi

Carmo, Mirian Silva do; Santos, Marcia Rodrigues dos; Cummings, Leda M.; Araya, Jorge E.; Yamauchi, Luci M.; Yoshida, Nobuko; Mortara, Renato Arruda; Silveira, José Franco da

doi:10.1016/s0020-7519(00)00170-3

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…We further characterized the SAP gene family, which was discovered in the course of screening an expression genomic library of T. cruzi with antisera to metacyclic trypomastigotes (9). Through BLASPN and BLASTP searches against the T. cruzi GeneDB database, we identified 39 full-length copies of SAP that are distributed in 33 contigs (length ranging from 7,117 to 234,085 nucleotides): 28 contigs showed a single copy, four contigs carried two copies, and one contig had three copies of SAP (Fig.…”

Section: Resultsmentioning

confidence: 99%

Molecular Characterization of Serine-, Alanine-, and Proline-Rich Proteins of Trypanosoma cruzi and Their Possible Role in Host Cell Infection

Baida¹,

Santos²,

Carmo³

et al. 2006

Infect Immun

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Section: Resultsmentioning

confidence: 99%

Molecular Characterization of Serine-, Alanine-, and Proline-Rich Proteins of Trypanosoma cruzi and Their Possible Role in Host Cell Infection

Baida¹,

Santos²,

Carmo³

et al. 2006

Infect Immun

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“…A common evolutionary strategy, employed by many unicellular eukaryotic parasites, is expansive development of a family of surface proteins, which lie at the interface between host and parasite. Examples include PfEMP1 ( Leech et al., 1984 ), RIFIN ( Kyes et al., 1999 ), and STEVOR ( Cheng et al., 1998 ) of Plasmodium falciparum , VIR of P. vivax ( del Portillo et al., 2001 ), variant surface glycoproteins (VSGs) of Trypanosoma brucei ( Schwede and Carrington, 2010 ), MASP ( El-Sayed et al., 2005 ) and SAP ( Carmo et al., 2001 ) of Trypanosoma cruzi , and SAGs of Toxoplasma gondii ( Kasper et al., 1983 ). Expression switching between family members allows parasites to display a series of antigenically distinct surfaces, posing challenges for the immune system and for rational development of vaccines.…”

Section: Introductionmentioning

confidence: 99%

Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria

Lau

Turner

Jespersen

et al. 2015

Cell Host & Microbe

152

296

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SummaryThe PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding.

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“…Members of the SAP multigene family are characterized by a high serine (7.2 to 11.7%), alanine (12.2 to 17.3%) and proline (7.06 to 13.5%) residue content [17]. SAP genes have been classified into four groups (SAP1 to SAP4) according to the presence of an endoplasmic reticulum (ER) and/or glycosylphosphatidylinositol (GPI) anchor-addition signal peptide(s).…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Trypanosoma cruzi SAP Proteins with Host-Cell Lysosome Exocytosis-Inducing Activity Required for Parasite Invasion

et al. 2013

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BackgroundTo invade target cells, Trypanosoma cruzi metacyclic forms engage distinct sets of surface and secreted molecules that interact with host components. Serine-, alanine-, and proline-rich proteins (SAP) comprise a multigene family constituted of molecules with a high serine, alanine and proline residue content. SAP proteins have a central domain (SAP-CD) responsible for interaction with and invasion of mammalian cells by metacyclic forms.Methods and FindingsUsing a 513 bp sequence from SAP-CD in blastn analysis, we identified 39 full-length SAP genes in the genome of T. cruzi. Although most of these genes were mapped in the T. cruzi in silico chromosome TcChr41, several SAP sequences were spread out across the genome. The level of SAP transcripts was twice as high in metacyclic forms as in epimastigotes. Monoclonal (MAb-SAP) and polyclonal (anti-SAP) antibodies produced against the recombinant protein SAP-CD were used to investigate the expression and localization of SAP proteins. MAb-SAP reacted with a 55 kDa SAP protein released by epimastigotes and metacyclic forms and with distinct sets of SAP variants expressed in amastigotes and tissue culture-derived trypomastigotes (TCTs). Anti-SAP antibodies reacted with components located in the anterior region of epimastigotes and between the nucleus and the kinetoplast in metacyclic trypomastigotes. In contrast, anti-SAP recognized surface components of amastigotes and TCTs, suggesting that SAP proteins are directed to different cellular compartments. Ten SAP peptides were identified by mass spectrometry in vesicle and soluble-protein fractions obtained from parasite conditioned medium. Using overlapping sequences from SAP-CD, we identified a 54-aa peptide (SAP-CE) that was able to induce host-cell lysosome exocytosis and inhibit parasite internalization by 52%.ConclusionsThis study provides novel information about the genomic organization, expression and cellular localization of SAP proteins and proposes a triggering role for extracellular SAP proteins in host-cell lysosome exocytosis during metacyclic internalization.

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Isolation and characterisation of genomic and cDNA clones coding for a serine-, alanine-, and proline-rich protein of Trypanosoma cruzi

Cited by 8 publications

References 32 publications

Molecular Characterization of Serine-, Alanine-, and Proline-Rich Proteins of Trypanosoma cruzi and Their Possible Role in Host Cell Infection

Molecular Characterization of Serine-, Alanine-, and Proline-Rich Proteins of Trypanosoma cruzi and Their Possible Role in Host Cell Infection

Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria

Molecular Characterization of Trypanosoma cruzi SAP Proteins with Host-Cell Lysosome Exocytosis-Inducing Activity Required for Parasite Invasion

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