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Identification of the minimal binding region of a Plasmodium falciparum IgM binding PfEMP1 domain.

Semblat JP, Ghumra A, Czajkowsky DM, Wallis R, Mitchell DA, Raza A, Rowe JA - Mol. Biochem. Parasitol. (2015)

Bottom Line: Here we studied an IgM binding domain from a rosette-mediating PfEMP1 variant, DBL4ζ of TM284var1, and found that the minimal IgM binding region mapped to the central region of the DBL domain, comprising all of subdomain 2 and adjoining parts of subdomains 1 and 3.Site-directed mutagenesis of charged amino acids within subdomain 2, predicted by molecular modelling to form the IgM binding site, showed no marked effect on IgM binding properties.Further work is needed to identify the specific interaction site for IgM within the minimal binding region of PfEMP1.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom.

No MeSH data available.


Related in: MedlinePlus

Homology model of TM284var1 DBL4ζ.The TM284var1 sequence starting from Glu1481 to Thr1952 was used to generate a model of DBL4ζ based on the structure of DBL6ϵ of 3D7var2CSA as described previously [16]. Amino acids 1595–1814, the minimal IgM binding region, are shown in orange. Negatively charged amino acids postulated to bind IgM are shown in red (Glu1663, Glu1665 and Glu1779, and positively charged residues in blue (Arg1764 and Lys1782).
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fig0010: Homology model of TM284var1 DBL4ζ.The TM284var1 sequence starting from Glu1481 to Thr1952 was used to generate a model of DBL4ζ based on the structure of DBL6ϵ of 3D7var2CSA as described previously [16]. Amino acids 1595–1814, the minimal IgM binding region, are shown in orange. Negatively charged amino acids postulated to bind IgM are shown in red (Glu1663, Glu1665 and Glu1779, and positively charged residues in blue (Arg1764 and Lys1782).

Mentions: DBL domains are composed of a core scaffold of alpha-helical bundles stabilised by disulphide bonds, and consist of three subdomains [21]. The minimal IgM binding region comprises all of subdomain 2 of TM284var1 DBLζ, with flanking parts of subdomain 1 and 3 (Fig. 1C). The minimal binding region is shown in orange in a homology model of the TM284var1 DBLζ domain (Fig. 2).


Identification of the minimal binding region of a Plasmodium falciparum IgM binding PfEMP1 domain.

Semblat JP, Ghumra A, Czajkowsky DM, Wallis R, Mitchell DA, Raza A, Rowe JA - Mol. Biochem. Parasitol. (2015)

Homology model of TM284var1 DBL4ζ.The TM284var1 sequence starting from Glu1481 to Thr1952 was used to generate a model of DBL4ζ based on the structure of DBL6ϵ of 3D7var2CSA as described previously [16]. Amino acids 1595–1814, the minimal IgM binding region, are shown in orange. Negatively charged amino acids postulated to bind IgM are shown in red (Glu1663, Glu1665 and Glu1779, and positively charged residues in blue (Arg1764 and Lys1782).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4539346&req=5

fig0010: Homology model of TM284var1 DBL4ζ.The TM284var1 sequence starting from Glu1481 to Thr1952 was used to generate a model of DBL4ζ based on the structure of DBL6ϵ of 3D7var2CSA as described previously [16]. Amino acids 1595–1814, the minimal IgM binding region, are shown in orange. Negatively charged amino acids postulated to bind IgM are shown in red (Glu1663, Glu1665 and Glu1779, and positively charged residues in blue (Arg1764 and Lys1782).
Mentions: DBL domains are composed of a core scaffold of alpha-helical bundles stabilised by disulphide bonds, and consist of three subdomains [21]. The minimal IgM binding region comprises all of subdomain 2 of TM284var1 DBLζ, with flanking parts of subdomain 1 and 3 (Fig. 1C). The minimal binding region is shown in orange in a homology model of the TM284var1 DBLζ domain (Fig. 2).

Bottom Line: Here we studied an IgM binding domain from a rosette-mediating PfEMP1 variant, DBL4ζ of TM284var1, and found that the minimal IgM binding region mapped to the central region of the DBL domain, comprising all of subdomain 2 and adjoining parts of subdomains 1 and 3.Site-directed mutagenesis of charged amino acids within subdomain 2, predicted by molecular modelling to form the IgM binding site, showed no marked effect on IgM binding properties.Further work is needed to identify the specific interaction site for IgM within the minimal binding region of PfEMP1.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom.

No MeSH data available.


Related in: MedlinePlus