Helix minor groove

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

Figure 8.22 The lac repressor molecule is a V-shaped tetramer in which each arm is a dimer containing a DNA-hinding site. The helix-tum-helix motifs (red) of each dimer bind in two successive major grooves and the hinge helices (purple) bind adjacent to each other in the minor groove between the two major groove binding sites. The four subunits of the tetramer are held together by the four C-terminal helices (yellow) which form a four helix bundle. The bound DNA fragments are bent. (Adapted from M. Lewis et al., Science 271 1247-1254, 1996.)...

Figure 8.23 The helix-turn-helix motifs of the subunits of both the PurR and the lac repressor subunits bind to the major groove of DNA with the N-terminus of the second helix, the recognition helix, pointing into the groove. The two hinge helices of each arm of the V-shaped tetramer bind adjacent to each other in the minor groove of DNA, which is wide and shallow due to distortion of the B-DNA structure. (Adapted from M.A. Schumacher et al.. Science 266 763-770, 1994.)...

Some of the procaryotic DNA-binding proteins are activated by the binding of an allosteric effector molecule. This event changes the conformation of the dimeric protein, causing the helix-tum-helix motifs to move so that they are 34 A apart and able to bind to the major groove. The dimeric repressor for purine biosynthesis, PurR, induces a sharp bend in DNA upon binding caused by insertion of a helices in the minor groove between the two... 

Most sequence-specific regulatory proteins bind to their DNA targets by presenting an a helix or a pair of antiparallel p strands to the major groove of DNA. Recognition of the TATA box by TBP is therefore exceptional it utilizes a concave pleated sheet protein surface that interacts with the minor groove of DNA. Since the minor groove has very few sequence-specific... 

Residues 3, 5, 6, and 8 in the N-terminal arm lie in the minor groove and form contacts with either the edge of the bases or with the DNA backbone. Almost all homeodomains contain four conserved residues, Asn 51, Arg 53, Trp 48 and Phe 49, in the middle of the long recognition helix. The first two conserved polar residues interact with DNA. The second two are part of the hydrophobic core of the homeodomain, and are important for the accurate positioning of the recognition helix and the N-terminal arm with respect to... 

Figure 9.10 Schematic diagrams illustrating the complex between DNA (orange) and one monomer of the homeodomain. The recognition helix (red) binds in the major groove of DNA and provides the sequence-specific interactions with bases in the DNA. The N-terminus (green) binds in the minor groove on the opposite side of the DNA molecule and arginine side chains make nonspecific interactions with the phosphate groups of the DNA. (Adapted from C.R. Kissinger et al Cell 63 579-590, 1990.)...

Figure 9.20 Diagram iliustrating the sequence-specific interactions between DNA and p53. The C-terminai a helix and loop LI of p53 bind in the major groove of the DNA. Arg 280 from the a helix and Lys 120 from LI form important specific interactions with bases of the DNA. In addition, Arg 248 from loop L3 binds to the DNA in the minor groove. (Adapted from Y. Cho et al.. Science 265 346-355, 1994.)...

The DNA helix has major and minor grooves Z-DNA forms a zigzag pattern B-DNA is the preferred conformation in vivo Specific base sequences can be recognized in B-DNA Conclusion Selected readings... 

Helix axis location Major groove Through base pairs Minor groove... 

TBP binds to the TATA box in the minor groove of DNA (most transcription factors bind in the major groove) and causes an approximately 100-degree bend or kink of the DNA helix. This bending is thought to facilitate the interaction of TBP-associated factors with other components of the transcription initiation complex and possibly with factors bound to upstream elements. Although defined as a component of class II gene promoters, TBP, by virtue of its association with... 

Fig. 12 (A) The d(CGCGAATTCGCG)2 duplex with a narrow groove and a sodium ion coordinated at the ApT step. (I) The DNA is shown in stick representation and the ion in space-filling size. Left view is directly into the central minor groove. Right view left view rotated 90° counterclockwise and tilted 30° to show the ion in the minor groove. (II) The base pair views are of the central ApT step. Top view is down the helix axis, bottom view is directly into the minor groove. (B) The DNA duplex with a phosphate-oxygen pair-sodium ion interaction and a water molecule coordinated at the ApT step. (II) Views as in Fig. 12A for the phosphate-ion-water-base complex at the AT site. Reproduced with permission from Ref. (42). Copyright 2000, American Chemical Society.

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