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Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells.

Human DNA helicase II (HDH II) is a novel ATP‐dependent DNA unwinding enzyme, purified to apparent homogeneity from HeLa cells, which (i) unwinds exclusively DNA duplexes, (ii) prefers partially unwound substrates and (iii) proceeds in the 3′ to 5′ direction on the bound strand. HDH II is a heterodimer of 72 and 87 kDa polypeptides. It shows single‐stranded DNA‐dependent ATPase activity, as well as double‐stranded DNA binding capacity. All these activities comigrate in gel filtration and glycerol gradients, giving a sedimentation coefficient of 7.4S and a Stokes radius of approximately 46 A, corresponding to a native molecular weight of 158 kDa. The antibodies raised in rabbit against either polypeptide can remove from the solution all the activities of HDH II. Photoaffinity labelling with [alpha‐32P]ATP labelled both polypeptides. Microsequencing of the separate polypeptides of HDH II and cross‐reaction with specific antibodies showed that this enzyme is identical to Ku, an autoantigen recognized by the sera of scleroderma and lupus erythematosus patients, which binds specifically to duplex DNA ends and is regulator of a DNA‐dependent protein kinase. Recombinant HDH II/Ku protein expressed in and purified from Escherichia coli cells showed DNA binding and helicase activities indistinguishable from those of the isolated protein. The exclusively nuclear location of HDH II/Ku antigen, its highly specific affinity for double‐stranded DNA, its abundance and its newly demonstrated ability to unwind exclusively DNA duplexes, point to an additional, if still unclear, role for this molecule in DNA metabolism.

Malaria is caused by protozoan parasites of the genus Plasmodium and is a major cause of mortality and morbidity worldwide. These parasites have a complex life cycle in their mosquito vector and vertebrate hosts. The primary factors contributing to the resurgence of malaria are the appearance of drug‐resistant strains of the parasite, the spread of insecticide‐resistant strains of the mosquito and the lack of licensed malaria vaccines of proven efficacy. This minireview includes a summary of the disease, the life cycle of the parasite, information relating to the genome and proteome of the species lethal to humans, Plasmodium falciparum, together with other recent developments in the field.

DNA helicases are molecular ÔmotorÕ enzymes that use the energy of NTP hydrolysis to separate transiently energetically stable duplex DNA into single strands. They are therefore essential in nearly all DNA metabolic transactions. They act as essential molecular tools for the cellular machinery. Since the discovery of the first DNA helicase in Escherichia coli in 1976, several have been isolated from both prokaryotic and eukaryotic systems. DNA helicases generally bind to ssDNA or ssDNA/dsDNA junctions and translocate mainly unidirectionally along the bound strand and disrupt the hydrogen bonds between the duplexes. Most helicases contain conserved motifs which act as an engine to drive DNA unwinding. Crystal structures have revealed an underlying common structural fold for their function. These structures suggest the role of the helicase motifs in catalytic function and offer clues as to how these proteins can translocate and unwind DNA. The genes containing helicase motifs may have evolved from a common ancestor. In this review we cover the conserved motifs, structural information, mechanism of DNA unwinding and translocation, and functional aspects of DNA helicases.Keywords: crystal structure; DEAD-box protein; DNA helicase; helicase motifs; unwinding enzyme.DNA helicases are motor proteins that can transiently catalyze the unwinding of energetically stable duplex DNA molecules using NTP hydrolysis as the source of energy [1,2]. They are important enzymatic tools for the cellular DNA machinery. They are known to play essential roles in nearly all aspects of nucleic acid metabolism, such as DNA replication, repair, recombination, and transcription. All helicases share at least three common biochemical properties: (a) nucleic acid binding; (b) NTP/dNTP binding and hydrolysis; (c) NTP/dNTP hydrolysis-dependent unwinding of duplex nucleic acids in the 3¢ to 5¢ or 5¢ to 3¢ direction [3]. Therefore, all DNA helicases described to date also have intrinsic DNA-dependent NTPase activity [4,5]. These enzymes usually act in concert with other enzymes or proteins in DNA metabolic activity. Multiple DNA helicases have been isolated from single-cell types because of different structural requirements of the substrate at various stages of the DNA transaction. For example, at least 14 different DNA helicases have been isolated from a simple single-cell organism such as Escherichia coli, six from bacteriophages, 12 from viruses, 15 from yeast, eight from plants, 11 from calf thymus, and as many as 24 from human cells. These have been described in the preceding review.Most helicases from many different organisms contain about nine short conserved amino-acid sequence fingerprints (designated Q, I, Ia, Ib, II, III, IV, V and VI), called Ôhelicase motifsÕ [6][7][8][9][10]. These motifs are usually clustered in a region of 200-700 amino acids called the core region. Because of the sequence of motif II (DEAD or DEAH or DEXH), the helicase family is also called the DEAD-box protein family. The crystal structures of some of the DNA hel...