Selective association of a fragment of the knob protein with spectrin, actin and the red cell membrane

Kilejian, Araxie; Rashid, M. A.; Aikawa, Masamichi; Aji, Toshiki; Yang, Yuesong

doi:10.1016/0166-6851(91)90003-o

Cited by 94 publications

(72 citation statements)

References 23 publications

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“…Thus, we localized a distinct spectrin-binding site in KAHRP to a 72-amino-acid region. This finding is in agreement with a previous report, which localized the spectrinbinding site in KAHRP to a much larger 271-amino-acid region that encompasses the domain we identified (27).…”

Section: Resultssupporting

confidence: 83%

“…It is interesting to note that the binding regions of MESA, RESA and MSP-1 mentioned above are all found in non-repetitive domains (33)(34)(35). Previous work that mapped the spectrin-binding domain of KAHRP to a 271-residue region (27), and this region contained the 5Ј-repeat. However, in the present study we found that K2A, which is composed of the complete 5Ј-repeat and 21 amino acids downstream of this 5Ј-repeat sequence did not bind spectrin.…”

Section: Discussionmentioning

confidence: 99%

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Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Pei

Guo

et al. 2005

Journal of Biological Chemistry

100

109

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Plasmodium falciparum dramatically modifies the structure and function of the membrane of the parasitized host erythrocyte. Altered membrane properties are the consequence of the interaction of a group of exported malaria proteins with host cell membrane proteins. KAHRP (the knob-associated histidine-rich protein), a member of this group, has been shown to interact with erythrocyte membrane skeletal protein spectrin. However, the molecular basis for this interaction has yet to be defined. In the present study, we defined the binding motifs in both KAHRP and spectrin and identified a functional role for this interaction. We showed that spectrin bound to a 72-amino-acid KAHRP fragment (residues 370 -441). Among nine-spectrin fragments, which encompass the entire ␣ and ␤ spectrin molecules (four ␣ spectrin and five ␤ spectrin fragments), KAHRP bound only to one, the ␣ N-5 fragment. The KAHRP-binding site within the ␣ N-5 fragment was localized uniquely to repeat 4. The interaction of fulllength spectrin dimer to KAHRP was inhibited by repeat 4 of ␣ spectrin. Importantly, resealing of this repeat peptide into erythrocytes mislocalized KAHRP in the parasitized cells. We concluded that the interaction of KAHRP with spectrin is critical for appropriate membrane localization of KAHRP in parasitized erythrocytes. As the presence of KAHRP at the erythrocyte membrane is necessary for cytoadherence in vivo, our findings have implications for the development of new therapies for mitigating the severity of malaria infection.Malaria caused by Plasmodium falciparum is the most serious parasitic disease of humans. Clinical symptoms occur during the asexual stage of the life cycle of the parasites, at which time it multiplies within the human erythrocyte. During intraerythrocytic growth, the parasite extensively modifies the host erythrocyte resulting in alterations of morphology, mechanical properties, and adhesive properties. It is generally believed that almost all the altered properties of parasitized erythrocytes are because of the action of a group of parasite proteins that become associated with erythrocyte membrane proteins (see Refs. 1-3 for recent reviews). Well studied members of this group include the knob-associated histidine-rich protein (KAHRP), 1 P. falciparum erythrocyte membrane protein 1 (PfEMP1), the ring parasite-infected erythrocyte surface antigen (RESA), and the mature parasite-infected erythrocyte surface antigen (MESA).KAHRP, an 85-105-kDa protein that is expressed during the middle and later stages of the asexual cycle (4, 5), has been shown to be critically important for knob formation in infected erythrocytes (6). It interacts with erythrocyte skeletal proteins such as spectrin, actin, and ankyrin (7, 8) and also with erythrocyte membrane-associated parasite protein, PfEMP1 (9). PfEMP1 mediates the adhesion of parasitized erythrocytes to the vascular endothelium (10), a process strongly implicated in the pathology of cerebral malaria (11). The absence of the KAHRP protein at the erythrocyte membrane l...

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Section: Resultssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Pei

Guo

et al. 2005

Journal of Biological Chemistry

100

109

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“…2 and ref. [4]). Except few minor point mutations, the first two domains were conserved among both the Indian isolates.…”

Section: Resultsmentioning

confidence: 99%

“…This protein is synthesized by ring and early trophozoite stages of the parasite [3]. KAHRP is then transported to the red cell membrane where it induces knobs by interacting with several host as well as parasite derived molecules [4]. Earlier, we have reported the cloning and sequencing of the KAHRP gene from a Gambian isolate FCR3 [3,5].…”

Section: Introductionmentioning

confidence: 99%

Allelic forms of the knob associated histidine‐rich protein gene of Plasmodium falciparum

Kant

Sharma

1996

FEBS Letters

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The knob associated histidine-rich protein (KAHRP) gene was cloned and sequenced from two Indian isolates of Plasmodiumfalciparum, Pf3-92 and Pf29-92. These isolates showed major sequence differences in the C-terminal repeat domain of KAHRP. However, the biologically important domains such as spectrin-actin binding region remained highly conserved. The PCR amplification of a variable C-terminal repeat domain from the clinical isolates of P. falciparum, from Rajasthan epidemic, showed the presence of multiple alleles of KAHRP gene. The presence of multiple alleles indicates the existence of several P. falciparum strains in India. This should be taken into account for future malaria control strategies such as molecular therapy and vaccines.

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“…Similarities in chemical characteristics, especially in charge distribution, were found between two peptides of PfHRP1 and the spectrin/ actin-binding domain of band 4.1. This fragment forms stable complexes in v i m with the two major cytoskeletal proteins, for binding of these proteins (Kilejian et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

An 88‐kDa protein of Plastmidium falciparum is related to the band‐3‐binding domain of human erythrocyte ankyrin

Suetterlin¹,

Kappes²,

Jenoe³

et al. 1992

European Journal of Biochemistry

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Three typtic‐peptide sequences of an 88‐kDa pair of phosphoproteins of the malaria parasite Plasmodium falciparum were determined. They exhibit a striking similarity to corresponding sequences of the 89‐kDa domain of human erythrocyte ankyrin. [35S]Methionine labeling of the two proteins demonstrated thier parasitic origin. Using an appropriate oligonucletide probe, Southern‐blot analysis of genomic malaria DNA and Norhtern‐blot analysis of malaria RNA suggest the existence of ankyrin‐related sequences in the parasite genome and the presence of an ankyrin‐related transcirpt of about 3.2 kb. Our studies provide further evidence of malaria‐specific analogues of host‐cell proteins, implying an unusual kind of parasite/host interaction.

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Selective association of a fragment of the knob protein with spectrin, actin and the red cell membrane

Cited by 94 publications

References 23 publications

Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin

Allelic forms of the knob associated histidine‐rich protein gene of Plasmodium falciparum

An 88‐kDa protein of Plastmidium falciparum is related to the band‐3‐binding domain of human erythrocyte ankyrin

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