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Extrapolating from the co-crystal structure of rat DNA polymerase β pol β) complexed with primer-template, dideoxycytidine triphosphate (DDCTP), and two metal ions, H. Pelletier et al. (1) recently concluded that [...]

The structure of HIV-1 reverse transcriptase reveals a peculiar aspect of polymerase domain, assuming a different structure in the two subunits p51 and p66. However, it has the same polypeptide chain sequence as other transcriptases. The two subunits interact to produce one polymerase cleft that binds primer-template.

Activation of the oncogenic potential of the MEK kinase TPL-2 (Cot) requires deletion of its C terminus. This mutation also weakens the interaction of TPL-2 with NF-κB1 p105 in vitro, although it is unclear whether this is important for the activation of TPL-2 oncogenicity. It is demonstrated here that TPL-2 stability in vivo relies on its high-affinity, stoichiometric association with NF-κB1 p105. Formation of this complex occurs as a result of two distinct interactions. The TPL-2 C terminus binds to a region encompassing residues 497 to 534 of p105, whereas the TPL-2 kinase domain interacts with the p105 death domain. Binding to the p105 death domain inhibits TPL-2 MEK kinase activity in vitro, and this inhibition is significantly augmented by concomitant interaction of the TPL-2 C terminus with p105. In cotransfected cells, both interactions are required for inhibition of TPL-2 MEK kinase activity and, consequently, the catalytic activity of a C-terminally truncated oncogenic mutant of TPL-2 is not affected by p105. Thus, in addition to its role as a precursor for p50 and cytoplasmic inhibitor of NF-κB, p105 is a negative regulator of TPL-2. Insensitivity of C-terminally truncated TPL-2 to this regulatory mechanism is likely to contribute to its ability to transform cells. [ABSTRACT FROM AUTHOR]

Focuses on a study which examined the role of the cross-talk between small-G protein families in signaling. Mechanism of Arfaptin (Arf) binding to guanosine triphosphate (GTP)-bound Arf1 and Arf6; Significance of the coordinated action of Arf and Rho family GTPases in cellular processes; X-ray structures of Arfaptin; Differences between the molecular mechanisms of Rho and Ras family signaling.