1. DExD/H Box RNA Helicases
N.Kyle Tanner, Patrick Linder 
Molecular Cell 
Volume 8, Issue 2, Pages (August 2001)
DOI: /S (01)00329-X

2. Figure 1 Conserved Sequence Motifs of RNA Helicases
(A) Positions of conserved motifs within eIF4A. The amino- and carboxyl-terminal extensions, before motif I and beyond motif VI, are 45 and 40 amino acids, respectively. This is close to the minimal size seen for an RNA or DNA helicase. Other RNA helicases can have amino- or carboxyl-terminal extensions greater than 500 amino acids. The Rep-like and UvrD-like DNA helicases are characterized by internal insertions, indicated as domain 1b and 2b, as well as a DNA helicase-specific motif IV* (shown in gray). Motif IV is known as IVa in DNA helicases (Korolev et al., 1998). Some RNA helicases derived their name from the characteristics of motif II (e.g., DEAD, DEAH), while others are named after a representative member (e.g., Ski2p, Upf1), as with DNA helicases. This figure is not drawn to scale.
(B) Alignments of the conserved motifs. Except for motifs I and II, the conserved motifs historically have been largely defined by the order of appearance of conserved amino acids relative to the Walker NTP binding motifs. Thus, the precise character of the motifs varies between families of helicases and between authors. Amino acids that occupy equivalent positions between families have only been determined where crystal structures are available, as for NS3 and the DEAD box proteins (Caruthers et al., 2000; Lin and Kim, 1999), but ambiguities remain, as for motifs III and IV for Upf1. Amino acids conserved at least 80% of the time are shown as capital letters while those conserved 50%–79% of the time are in lower case. Note that there are additional, highly conserved amino acids outside of the sequences shown that are often family specific
Molecular Cell 2001 8, DOI: ( /S (01)00329-X)

3. Figure 2 Three-Dimensional Structures of RNA and DNA Helicases
(A) The core structures, as defined by eIF4A, are shown as ribbons and cords; positions of insertions and extensions are indicated with arrows. An ATP is shown bound within the P loop of PcrA; a sulfate is shown in the equivalent position of NS3 and MjDEAD. The motifs are shown in different colors (as in Figure 1) and indicated by roman numerals. Amino acids in motif IV of NS3 were not all resolved in the crystal structure and are shown as a gap. To facilitate comparisons, motifs are aligned relative to conserved amino acids defined by Lin and Kim (1999) and Caruthers et al. (2000). Note that Rep-like and UvrD-like helicases have an extra motif IV, indicated as IV*, that is not found in the RNA helicases. Only a portion of the DNA substrate is shown for PcrA.
(B) The fragment of NS3 that has RNA helicase activity in vitro. The amino-terminal one-third of the protein, which contains a serine-protease activity, was removed to facilitate crystallization. The PDB coordinates used were 1A1V for HCV NS3 (Kim et al., 1998), 3PJR for Bacillus stearothermophilus PcrA (Velankar et al., 1999), and 1HV8 for Methanococcus janaschii MjDEAD (Story et al., 2001), and they were obtained from the authors or through Research Collaboratory for Structural Bioinformatics (RCSB; Berman et al., 2000). The PDB coordinates were modeled on the Macintosh with Swiss-PdbViewer (Guex and Peitsch, 1997); and the images rendered with POV-Ray (
Molecular Cell 2001 8, DOI: ( /S (01)00329-X)

4. Figure 3 Models of Helicase Activity
The active rolling model requires at least a dimerized helicase in which each monomer has a different conformational state and affinity for single-stranded and double-stranded nucleic acids. These conformations vary with NTP binding and hydrolysis. It proposes a step size that is equivalent to the binding-site size or 8–10 bases. Note that the handiness shown is used to distinguish between subunits, and it should not be inferred that the subunits are mirror images of each other. The inchworm model works with a monomer or oligomer state. In this case, the distance between domains 1 and 2 vary with NTP binding and hydrolysis. Specific amino acids, shown as the feet of the inchworm (or caterpillar) form nonspecific interactions with the sugar-phosphate backbone, or they stack or intercalate against the bases; these latter interactions act as teeth to help maintain the positions of domains rather like the sprocket of a ratchet. This provides a mechanism to ensure that the helicase moves with a specific polarity. These models are described in more detail in the text
Molecular Cell 2001 8, DOI: ( /S (01)00329-X)

5. Figure 4
Ribosome and Spliceosome Assembly Are Highly Dynamic Processes
(A) Eukaryotic ribosome is highly conserved from yeast to humans. In yeast, the rDNA is transcribed as a 35S pre-rRNA precursor. This precursor is modified by methylation and pseudo-uridylation reactions. The modifications and the early cleavage reactions at sites A0, A1, and A2 take place in a large 90S preribosomal particle. Cleavage at A2 allows splitting of the 90S particle into two precursors that will mature into the 40S and 60S subunits. Maturation of the 40S subunit involves export into the cytoplasm and maturation of the 20S pre-rRNA into the mature 18S rRNA. The maturation of the 60S subunit involves several processing reactions resulting in the mature 5.8S and 25S rRNAs. Endonucleolytic and exonucleolytic reactions are indicated by red and green arrows, respectively. RNA helicases (yellow boxes) of the DExD/H families play essential roles in these maturation steps. The helicases Has1p, Mak5p, and Drs1p have not been attributed to a particular step.
(B) Nuclear pre-RNA splicing involves several steps that depend on the activity of DExD/H RNA helicases (yellow boxes). For splicing to occur, several snRNP complexes (green circles) transiently and sequentially associate with the pre-mRNA
Molecular Cell 2001 8, DOI: ( /S (01)00329-X)