Polypeptide Chain Binding Proteins

Molecular chaperones, stress proteins (note not all stress proteins are molecular chaperones and not all molecular chaperones are stress proteins) Heat shock proteins (Hsp) Polypeptide chain binding proteins... 

Some proteins, especially those destined for the eukaryotic mitochondria and chloroplasts, are transported after their synthesis on free polysomes is complete. Such transport is known as posttranslational transport. In the case of posttranslational transport it is believed that the polypeptide to be transported must be unfolded from its native folded configuration by a system of polypeptide-chain-binding proteins (PCBs) before it can pass through the membrane. Posttranslational transport into the mitochondrion requires both ATP and a proton gradient. Presumably the energy from one or both of these sources is used to unfold the protein or separate it from the PCB system so that it can pass through the membrane. 

Rothman, J. E., Polypeptide chain binding proteins Catalysts of protein folding and related processes in cells. Cell 59 591, 1989. A description of the proteins that are thought to be involved promoting the formation of three-dimensional structure in proteins. 

Rothman JE (1989) Polypeptide chain binding proteins catalysts of proteins folding and related processes in cells. Cell 59 591-601 Sanchez Y, Taulien J, Borkovich KA, Lindquist S (1992) Hspl04 is required for tolerance to many forms of stress. EMBO J 11 2357-2364 Sanders BM (1990) Stress proteins potential as multitiered biomarkers. In McCarthy J, Shugart L (eds) Biological markers of environmental contamination. Lewis, Boca Raton, pp 165-191... 

The fundamental unit of tertiary structure is the domain. A domain is defined as a polypeptide chain or a part of a polypeptide chain that can fold independently into a stable tertiary structure. Domains are also units of function. Often, the different domains of a protein are associated with different functions. For example, in the lambda repressor protein, discussed in Chapter 8, one domain at the N-terminus of the polypeptide chain binds DNA, while a second domain at the C-terminus contains a site necessary for the dimerization of two polypeptide chains to form the dimeric repressor molecule. 

Any set of geometrically and energetically equivalent binding interactions between two identical polypeptide chains or proteins. In a homophilic interaction, one polypeptide chain serves as a ligand for a receptor site on the other polypeptide chain, and vice versa. 

Polypeptides with more than a few hundred amino acid residues often fold into two or more stable, globular units called domains. In many cases, a domain from a large protein will retain its correct three-dimensional structure even when it is separated (for example, by proteolytic cleavage) from the remainder of the polypeptide chain. A protein with multiple domains may appear to have a distinct globular lobe for each domain (Fig. 4-19), but, more commonly, extensive contacts between domains make individual domains hard to discern. Different domains often have distinct functions, such as the binding of small molecules or interaction with other proteins. Small proteins usually have only one domain (the domain is the protein). 

Kassenbrock, C. K., Garcia, P. D., Walter, P., and Kelly, R, B. (1988). Heavy-chain binding protein recognizes aberrant polypeptides translocated in vitro. Nature (London) 333, 90-93. 

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 compound has two asymmetric centres (Fig. 22.48) but only diastereoisomer the R,R-isomer demonstrates significant antibacterial activity. Chloramphenicol binds to the SOS subunit and inhibits the bacterial enzyme peptidyl transferase. This prevents the growth of the polypeptide chain during protein synthesis. 

Parvalbumin is a muscle protein with a single polypeptide chain of 109 amino acids. Its function is uncertain, but calcium binding to this protein probably plays a role in muscle relaxation. The helix-loop-helix motif appears three times in this structure, in two of the cases there is a calcium-binding site. Figure 2.13 shows this motif which is called an EF hand because the fifth and sixth helices from the amino terminus in the structure of parvalbumin, which were labeled E and F, are the parts of the structure that were originally used to illustrate calcium binding by this motif. Despite this trivial origin, the name has remained in the literature. 

Figure 2.19 Organization of polypeptide chains into domains. Small protein molecules like the epidermal growth factor, EGF, comprise only one domain. Others, like the serine proteinase chymotrypsin, are arranged in two domains that are required to form a functional unit (see Chapter 11). Many of the proteins that are involved in blood coagulation and fibrinolysis, such as urokinase, factor IX, and plasminogen, have long polypeptide chains that comprise different combinations of domains homologous to EGF and serine proteinases and, in addition, calcium-binding domains and Kringle domains.

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

Figure 4.21 The polypeptide chain of the arabinose-binding protein in E. coli contains two open twisted a/P domains of similar structure. A schematic diagram of one of these domains is shown in (a). The two domains are oriented such that the carboxy ends of the parallel P strands face each other on opposite sides of a crevice in which the sugar molecule binds, as illustrated in the topology diagram (b). [(a) Adapted from J. Richardson.)...

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