Sequence-defined structures

Hays FA, Teegarden AT, Jones ZJR, Harms M, Raup D, Watson J, Cavaliere E, Ho PS. How does sequence define structure A crystallographic map of DNA structure and conformation. Proc. Natl. Acad. Sci. U.S.A. 2005 102 7157-7162. 

Keywords Biocompatible hydrogels Complex architectures Functionalized vinyl monomers lanus-type dendrimers Modular nature Passerini three-component reaction PEGylation of proteins Photo-responsive polymers Sequence-defined structures Tailor-made materials Ugi four-component reaction... 

ChemSketch has some special-purpose building functions. The peptide builder creates a line structure from the protein sequence defined with the typical three-letter abbreviations. The carbohydrate builder creates a structure from a text string description of the molecule. The nucleic acid builder creates a structure from the typical one-letter abbreviations. There is a function to clean up the shape of the structure (i.e., make bond lengths equivalent). There is also a three-dimensional optimization routine, which uses a proprietary modification of the CHARMM force field. It is possible to set the molecule line drawing mode to obey the conventions of several different publishers. 

In some cases, whole parts of the protein are missing from the experimentally determined structure. At times, these omissions reflect flexible parts of the molecule that do not have a well-defined structure (such as loops). At other times, they reflect parts of the molecule (e.g., terminal sequences) that were intentionally removed to facilitate the crystallization process. In both cases, structural models may be used to fill in the gaps. 

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

The recognition of positioning sequences has also made possible the construction of minichromosomes of regular defined structure (e.g., Ref. [44]), and reconstituted nucleosomes containing a defined DNA sequence. This latter advance was essential for the high-resolution X-ray diffraction studies of nucleosomes that have been accomplished (see Section 2.1). Defined minichromosomes have proved a powerful tool in many studies for a recent example, see Fan et al. [45]. 

DNA-binding proteins contact their recognition sequences via defined structural elements, termed DNA-binding motifs (overview Pabo Sauer, 1992 Burley, 1994). DNA-binding motifs are often found in structural elements of the protein which can fold independently from the rest of the protein and therefore represent separate DNA-binding domains. They can, however, also occur within sequence elements which can not independently fold, but whose folding depends on the tertiary structure of the rest of the protein. 

Transcription initiation in procaryotes is controlled via promoters and regulatory DNA sequences located near the promoter. The role of the promoter is to provide a defined association site for the RNA polymerase and to correctly orient it. The binding of the RNA polymerase to its promoter is controlled by the sigma factor, a component of the RNA polymerase holoenzyme. The sigma factor selects which genes are to be transcribed by specifically recognizing the promoter sequence and structure and by allowing the RNA polymerase to form a transcription-competent complex at the transcription start site. 

The TATA box and/or an initiation sequence are structural elements which define a minimal promoter from which in vitro transcription can be initiated. A classical TATA box is often, though not always, ca. 30bp from the transcription start site. The initiation sequence includes sequences in the immediate vicinity of the transcription start site. The TATA box and initiation sequence are sufficient for the formation of a basal transcription apparatus composed of general initiation factors for transcription and RNA polymerase II (see Fig. 1.31). 

Quaternary structure refers to the specific aggregation or association of separate protein chains to form a well-defined structure. Part D of Figure 2.4 compares the quaternary structure of a dimeric protein (two polypeptide chains) to the lower levels of protein structure. The separate protein chains are often referred to as subunits or monomers these subunits may be identical or may be of quite different sequence... 

It should be emphasized that copolymerizations that conform to the premises of binary-copolymerization theory produce copolymers of well defined structure. The kinetics of the competitive propagation-reactions determine not only the copolymer composition but also the sequence distribution. The mathematical procedures needed for calculating number-average sequence-lengths of mers, and sequence length-distributions of mers, are well known and have been... 

Aptamers are nucleic acids which exhibit a defined structure due to their nucleotide sequence and therefore, are able to specifically bind selected targets [1] (aptus [lat.] = fitting, sticking to). Aptamers and likewise, ribozymes [2] and deoxyribozymes [3] are selected in vitro by screening nucleic acid libraries. Here we describe in detail the selection of aptamers by a process called SELEX (Systematic Evolution of Ligands by Exponential enrichment) [4]. 

Design sequences with well defined structures, like this ... 

The options -Fmp tell RNAinverse to optimize the frequency of the MFE structure in the ensemble. The final sequence now has an extremely well-defined structure, as you can check by looking at the dot plot (gv dot. ps). 

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