Motif formation

Beijer FH, Sijbesma RP, Kooijman H, Spek AL, Meijer EW. Strong dimerization of ureidopyr-imidones via quadruple hydrogen bonding. Self-assembly mediated by the donor-donor-acceptor acceptor-acceptor-donor (DDA-AAD) hydrogen-bonding motif formation of a robust hexameric aggregate. J Am Chem Soc 1998 120 6761-6769. 

The structure of the heterodimeric transcription factor Fos/Jun bound to DNA has been solved. Jun contains a basic leucine zipper (bZIP) motif. Formation of a stable heterodimer is necessary for binding to DNA (see below). 

S. V. Kolotuchin, S. C. Zimmerman, Self-Assembly Mediated by the Donor-Donor-AcceptorAcceptor-Acceptor-Donor (DDAAAD) Hydrogen-Bonding Motif Formation of a Robust Hexameric Aggregate. /. Am. Chem. Soc. 1998,120, 9092-9093. 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Secondary structure occurs mainly as a helices and p strands. The formation of secondary structure in a local region of the polypeptide chain is to some extent determined by the primary structure. Certain amino acid sequences favor either a helices or p strands others favor formation of loop regions. Secondary structure elements usually arrange themselves in simple motifs, as described earlier. Motifs are formed by packing side chains from adjacent a helices or p strands close to each other. 

Figure 8.7 The N-terminal domains of lambda repressor form dimers, in spite of the absence of the C-terminal domains that are mainly responsible for dimer formation in the intact repressor. The dimers are formed by interactions between a helix 5 from each subunit. The different subunits are colored green and brown, except the helix-turn-hellx motif, which is colored blue and red as in Figure 8.4. (Adapted from C. Pabo and M. Lewis, Nature 298 443-447, 1982.)...

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

FIGURE 5.8 Two structural motifs that arrange the primary structure of proteins into a higher level of organization predominate in proteins the a-helix and the /3-pleated strand. Atomic representations of these secondary structures are shown here, along with the symbols used by structural chemists to represent them the flat, helical ribbon for the a-helix and the flat, wide arrow for /3-structures. Both of these structures owe their stability to the formation of hydrogen bonds between N—H and 0=C functions along the polypeptide backbone (see Chapter 6). 

Interestingly, certain other pore-forming toxins possess helix-bundle motifs that may participate in channel formation, in a manner similar to that proposed for colicin la. For example, the S-endotoxui produced by Bacillus thuringiensis is toxic to Coleoptera insects (beetles) and is composed of three domains, including a seven-helix bundle, a three-sheet domain, and a /3-sandwich. In the seven-helix bundle, helix 5 is highly hydrophobic, and the other six helices are amphipathic. In solution (Figure 10.32), the six amphipathic... 

Formation of a novel binding site novel complexes may be formed between a SUMOylated protein and an effector protein that contains a SUMO-interacting motif (SIM or SBM). Proteins that contain two binding sites, a SIM and a weak binding motif to protein X, will bind more strongly to this protein if it is SUMOylated (Fig. 3b). Short peptides that contain the hydrophobic core motif [V/I]-X-[V/I]-[V/I] or [V/I-[V/I]]-X-[V/I] can act as a SIM and bind to SUMO. This core is often flanked by acidic amino acids and/or serine residues. 

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