Fold into Complex Three-Dimensional Structures

The Cell Is the Fundamental Unit of Life Cells Are Composed of Small Molecules, Macromolecules, and Organelles Macromolecules Fold into Complex Three-Dimensional Structures... 

Macromolecules Fold into Complex Three-Dimensional Structures... 

As another example of polarity effects on macromo-lecular structure, consider polypeptide chains, which usually contain a mixture of amino acids with hydrophilic and hydrophobic side chains. Enzymes fold into complex three-dimensional globular structures with hydrophobic residues located on the inside of the structure and hydrophilic residues located on the surface, where they can interact with water (fig. 1.12). 

With the exception of structural proteins, which often remain linear, the polypeptide chains of proteins usually fold into complex, three-dimensional conformations. In enzymes, these conformations bring together certain functional groups of amino acids that are distantly located in the chain, so as to delimit specific binding sites and catalytic centers, disposed in such a manner that reaction substrates are fished out from the surrounding medium, immobilized in a particular configuration, and caused to interact. In addition, many enzymes also bear separate sites, called allosteric, which bind regulatory substances that modify the enzyme s functional properties. 

The tertiary structure of large complex proteins is often described in terms of physically independent regions called structural domains. You can usually identify domains from visual examination of a three-dimensional figure of a protein, such as the three-dimensional figure of G-actin shown in Fig. 7.9. Each domain is formed from a continuous sequence of amino acids in the polypeptide chain that are folded into a three-dimensional structure independently of the rest of the protein, and two domains are connected through a simpler structure like a loop (e.g., the hinge region of Fig. 7.9). The structural features of each domain can be discussed independently of another domain in the same protein, and the structural features of one domain may not match that of other domains in the same protein. 

The most widely recognized secondary structure for a biopolymer is the DNA double helix. However, DNA is capable of forming a variety of nonduplex secondary structures either transiently or at equilibrium. Moreover, the structural landscape available to RNA is vast, because RNA normally exists in the absence of a complementary strand. This allows RNA to fold into complex three-dimensional shapes, analogous to proteins, and exhibit many diverse functions. This section reviews the primary, secondary, and tertiary structures adopted by polynucleotides. 

Self-splicing KNA. The precursor to the 26S rRNA of Tetrahymena contains a 413-nucleotide intron, which was shown by Cedi and coworkers to be selfsplicing, i.e., not to require a protein catalyst for maturation.581 582 This pre-rRNA is a ribozyme with true catalytic properties (Chapter 12). It folds into a complex three-dimensional structure which provides a binding site for free guanosine whose 3-OH attacks the phosphorus at the 5 end of the intron as shown in Fig. 28-18A, step a. The reaction is a simple displacement on phosphorus, a transesterification similar to that in the first step of pancreatic ribonuclease action (Eq. 12-25). The resulting free 3-OH then attacks the phosphorus atom at the other end of the intron (step b) to accomplish the splicing and to release the intron as a linear polynucleotide. The excised intron undergoes... 

The structure of DNA revealed how information is stored in the base sequence along a DNA strand. But what information is stored and how is this information expressed The most fundamental role ol 1 )NA is to encode the sequences of proteins. Like DNA, proteins are linear polymers. 1 lowever. proteins differ from DNA in two important ways. First, proteins are built from 20 building blocks, called ammo acids, rather than just four, as are present in L NA. The chemical complexity provided by this variety of building blocks enables proteins to perform a wide range of functions. Second, proteins spontaneously fold up into elaborate three-dimensional structures, determined only by their amino acid sequences (Figure LI9). We have explored in depth how solutions containing two appropriate... 

As you might expect, the structures of extremely large molecules, such as proteins, are much more complex than those of simple organic compounds. Many protein molecules consist of a chain of amino acids twisted and folded into a complex three-dimensional structure. This structural complexity imparts unique features to proteins that allow them to function in the diverse ways required by biological systems. To better understand protein function, we must look at four levels of organization in their structure. These levels are referred to as primary, secondary, tertiary, and quaternary. 

Nature is replete with examples of functional nanostructures capable of completing complex tasks. These structures are composed of well-defined linear polymer chains folded into precise, three-dimensional shapes. An obvious yet unmet goal of chemists is to reproduce the functionality of natural systems using synthetic polymers. This warrants a tour de force involving modern controlled polymerization techniques and postpolymerization modification strategies in combination with current theories of polymer physics. Areas such as catalysis,sensing, nanoreactors, and nanomedicine ° stand to benefit from advances in this research. 

The process through which a linear string of amino acid residues newly synthesized at a ribosome folds into a complex, three-dimensional, biologically active protein structure remains poorly understood. Consider how protein-folding contrasts with RNA-folding. Proteins have 20 distinct monomeric units, RNA only four. The amino acids include aromatic, hydrophobic, cationic, and anionic chemical properties compared to four comparable RNA nucleosides. Moreover, secondary and tertiary structures were fundamentally inter-linked in proteins, but are essentially distinct in RNA molecules. 

The functional properties of proteins, like those of other biomolecules, are determined by their three-dimensional structures. Proteins possess an extremely important property a protein spontaneously folds into a welldefined and elaborate three-dimensional structure that is dictated entirely by the sequence of amino acids along its chain (Figure 1.6). The self-folding nature ofproteins constitutes the transition from the one-dimensional world of sequence information to the three-dimensional world of biological function. This marvelous ability of proteins to self assemble into complex... 

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