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Plasmodium falciparum glutamic acid-rich protein (PfGARP) is a recently characterized cell surface antigen encoded by Plasmodium falciparum , the causative agent of severe human malaria pathophysiology. Previously, we reported that the human erythrocyte band 3 (SLC4A1) serves as a host receptor for PfGARP. Antibodies against PfGARP did not affect parasite invasion and growth. We surmised that PfGARP may play a role in the rosetting and adhesion of malaria. Another study reported that antibodies targeting PfGARP exhibit potent inhibition of parasite growth. This inhibition occurred without the presence of any immune or complement components, suggesting the activation of an inherent density-dependent regulatory system. Here, we used polyclonal antibodies against PfGARP and a monoclonal antibody mAb7899 to demonstrate that anti-PfGARP polyclonal antibodies, but not mAb7899, exerted potent inhibition of parasite growth in infected erythrocytes independent of PfGARP. These findings suggest that an unknown malaria protein(s) is the target of growth arrest by polyclonal antibodies raised against PfGARP. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin [alpha]1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/ KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)[P.sub.2]). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule. kinesin | forkhead-associated domain | vesicle transport | phosphatidylinositol triphosphate | neuronal development doi/ 10.1073/pnas.1009008107

Phosphatidylinositol-(3,4,5)-trisphosphate (PI[P.sub.3]), a product of phosphatidylinositol 3-kinase, is an important second messenger implicated in signal transduction and membrane transport. In hippocampal neurons, the accumulation of PI[P.sub.3] at the tip of neurite initiates the axon specification and neuronal polarity formation. We show that guanylate kinase--associated kinesin (GAKIN), a kinesin-like motor protein, directly interacts with a PI[P.sub.3]-interacting protein, PI[P.sub.3]BP, and mediates the transport of PI[P.sub.3]-containing vesicles. Recombinant GAKIN and PI[P.sub.3]BP form a complex on synthetic liposomes containing PI[P.sub.3] and support the motility of the liposomes along microtubules in vitro. In PC12 cells and cultured hippocampal neurons, transport activity of GAKIN contributes to the accumulation of PI[P.sub.3] at the tip of neurites. In hippocampal neurons, altered accumulation of PI[P.sub.3] by overexpression of GAKIN constructs led to the loss of the axonally differentiated neurites. Together, these results suggest that, in neurons, the GAKIN-PI[P.sub.3]BP complex transports PI[P.sub.3] to the neurite ends and regulates neuronal polarity formation.

The recombinant form of the third PDZ domain of the human homolog of Drosophila discs-large tumor-suppressor gene product, DlgA, comprises a 5-stranded antiparallel beta-barrel surrounded by three alpha-helices. The domain's crystal structure includes a groove over its surface, which ends in a conserved hydrophobic pocket with arginine. This pocket is the binding site for the C-terminal peptide. PDZ domains are residue repeats located in a number of proteins. They help in ion-channel and receptor clustering, and linking of receptors to effector enzymes.

Peripheral membrane proteins dematin and protein 4.2 do not share structural and functional properties and are located away from each other in the membrane to negate any interaction. Dematin's 52 kDa subunit however shares a characteristic with protein 4.2, which is an 11-amino acid motif that has a nucleotide binding P-loop. The 11-amino acid motif is responsible for the specific, saturable and high affinity binding of ATP to dematin and protein 4.2.