Hairpins, protein structure

The hairpin (i motif occurs frequently in protein structures... 

Figure 5.10 Idealized diagrams of the Greek key motif. This motif is formed when one of the connections of four antiparallel fi strands is not a hairpin connection. The motif occurs when strand number n is connected to strand + 3 (a) or - 3 (b) instead of -r 1 or - 1 in an eight-stranded antiparallel P sheet or barrel. The two different possible connections give two different hands of the Greek key motif. In all protein structures known so far only the hand shown in (a) has been observed.

Large portions of most protein structures can be described as stretches of secondary structure (helices or /3 strands) joined by turns, which provide direction change and offset between sequence-adjacent pieces of secondary structure. Tight turns work well as a-a and a-fi joints, but their neatest application is at a hairpin connection... 

To say that RNA molecules are single-stranded molecules is not the same as saying that they have no higher-order structures, hi fact they have several. The formation of Watson-Crick complementary base pairs is a driving force for formation of higher-order structures. These include the stem-loop and hairpin secondary structures, as well as more complex tertiary structures. Of particular note, are the complex structures for transfer RNAs, tRNAs. Examples are provided in figure 12.5 (note that there are several nnnsnal bases in these structnres this is typical of tRNAs but not of RNA molecnles in general). These strnctures are intimately related to the function of these molecnles as adaptors in the process of protein synthesis, as developed in the next chapter. 

High resolution X-ray analysis of protein structures shows that the conformational categories of the connecting peptides which link the a-helices and -sheets are limited. Such well defined types of folding units, such as aa- and PP-hairpins, and aP- and Pa-arches, are referred to as supersecondary structures. One important step towards building a tertiary structure from secondary structures is to identify these supersecondary structure... 

Fasan, R., Dias, R.L.A., Moehle, K., Zerbe, O., Obrecht, D., Mittl, P.R.E., Grutter, M.G., and Robinson, JA. (2006) Structure-activity studies in a family of p-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. ChemBioChem. 7, 515-526. 

B. L. Sibanda, J. M. Thornton. Conformation of beta hairpins in protein structures classification and diversity in homologous structures. Methods Enzymol. 1991, 202, 59-82. 

Fasan R et al (2006) Structure-activity studies in a family of beta-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. Chembiochem 7(3) 515—526... 

H-protein structure. The H-protein also contains two additional /3-strands at the N-terminus, and a short helix at the C-terminus, rendering it significantly larger than the lipoyl domains of the E2 subunits of the PDC and KDC. The lipoyl group is covalently attached to a lysine residue that resides at the tip of a /3-hairpin structure, and in its reduced form is exposed to solvent, allowing it to interact with the L-protein to be reoxidized. By contrast, the structure of H-protein containing a methylaminated lipoyl group showed the cofactor to be locked in a cavity in the protein. " ... 

Structural model of the complex of the 3,6,9-trisubstituted acridine ligand (3) with the intramolecular basket quadruplex structure of the human telomeric sequence, (a) End-stacking with the terminal G-tetradpermits the substituent at the 9-position to interact with the flexible TTA loop structure in a specific manner, (b) X-ray structure of the complex of a di-substituted aninoalkylamido acridine (4) with the dimeric hairpin quadruplex structure derived from the Oxytricha nova sequence d(GGGGTTTTGGGG)2. The drug end-stacks and interacts extensively with the thymine loop ((a) Adapted from ref 25 and (b) from RCSB Protein Data Bank co-ordinates ILIH (ref 49)). 

How are RNA secondary structures involved in transcription attenuation In prokaryotes, transcrip)-tion and translation are linked. With attenuation, the RNA being transcribed is also being translated. Depending on the speed of simultaneous translation, the RNA produced can form different hairpin loop structures. In one orientation the hairpin loop acts as a terminator and aborts the transcription before the actual proteins can be translated. In another orientation the transcription is allowed to proceed. 

Because symmetry is a recurring theme for protein-DNA interactions, the DNA sequence may have functional importance. One possibility is that the DNA sequence could be a binding site for a dimeric regulatory protein. Alternatively, inverted repeat sequences sometimes serve as hot spots for genetic rearrangements because they may form hairpin secondary structures that block DNA polymerases or are processed by structure-specific endonucleases. 

The ability of proline to adopt a cis conformation in its peptide bond, for example, can create hairpin turns along the length of the protein. The thio groups of a cysteine side chain can be oxidized to form a covalent disulfide bridge between two adjacent cysteines. Disulfide bridges stabilize protein structure and can form large loops in proteins. 

A description of the protein-structure hierarchy is incomplete without a discussion of structural motifs, which are critical to an understanding of protein structure [17]. Identification of recurring motifs in protein structures has refined our knowledge of the protein-structure hierarchy these motifs occur at all levels from primary to tertiary. The Phe-Asp-Thr-Gly-Ser sequence found in the active site of all aspartic acid proteinases, and the Gly-Gly-X-Leu sequence (where X represents any amino acid residue) that predicts a 3-strand for the last two residues [17], are examples of sequence motifs a-helices, P-strands, and turns are examples of secondary-structural motifs PaP and PxP units, P-hairpins, and Greek keys are examples of supersecondary-structural motifs and four-a-helix bundles and TIM barrels are examples of tertiary-structural motifs. The tertiary fold of a protein is characterized by its tertiary-structural motif. 

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