Aggregation of polypeptide chains

Gastric or intestinal digestion Cellular protein turnover Post-mortem tenderization of meat Aggregation of polypeptide chains Blood clotting Activation of precursors Complement action Cleavage of presecretory proteins... 

The chemical polymerization of even a moderately sized protein of a hundred amino acids in the laboratory is extremely laborious, and the yields of active product can often be low to zero (Kent and Parker, 1988). Cells accomplish this task by using an intricate mechanism which involves catalytic machinery composed of proteins, nucleic acids and their complexes, and synthesize polypeptide chains that are composed of hundreds of amino acids. This process is depicted in Fig. 2.4, and is described in the sections below. The basic components of the cellular protein synthesis apparatus, in all known biological systems, are ribosomes, which are aggregate structures containing over fifty distinct proteins, and three distinct molecules of nucleic acid known as ribosomal ribonucleic acid (ribosomal RNA or rRNA). The amino acids are brought to the ribosomes, the assembly bench , by an RNA molecule known appropriately as transfer RNA . Each of the twenty amino acids is specifically coupled to a set of transfer RNAs (discussed below) which catalyze their incorporation into appropriate locations in the linear sequence of polypeptide chains. Several other intracellular proteins known as init iation and elongation factors a re also required for protein synthesis. 

The generic tendency of proteins to aggregate into nonfunctional, and sometimes cytotoxic, structures poses a universal problem for all types of cells. This problem is exacerbated by the high total concentrations of macromolecules found within most intracellular compartments, but it is solved by the actions of certain proteins that function as molecular chaperones. Different chaperones act by distinct mechanisms on both the folding of polypeptide chains and their subsequent assembly into oligomeric structures. Many chaperones, but not all, are also stress (or heat shock) proteins because the need for a chaperone function increases under stress conditions that cause proteins to unfold. 

Fig. 12. Possible forms of polypeptide chains in cross j3 configuration. A, super-folding of a single long chain B, aggregation of a number of shorter chains.

The special interest in cross patterns is that they could be interpreted as a superfolding of polypeptide chains as in Fig. 12A. The only indication that this is so depends on their association with the process of thermal contraction in systems with long fibrous molecules, e.g., fibrinogen, myosin, epidermin, and the fact that by high stretching cross 8 systems can be extended to the parallel d form (49). The alternative explanation is that they may be due to aggregation of shorter polypeptide chains in the backbone direction as in Fig. 12B (7). Probably the best means of arriving at the correct answer is by the study of the frictional... 

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...

The asymmetric unit contains one copy each of the subunits VPl, VP2, VP3, and VP4. VP4 is buried inside the shell and does not reach the surface. The arrangement of VPl, VP2, and VP3 on the surface of the capsid is shown in Figure 16.12a. These three different polypeptide chains build up the virus shell in a way that is analogous to that of the three different conformations A, C, and B of the same polypeptide chain in tomato bushy stunt virus. The viral coat assembles from 12 compact aggregates, or pen tamers, which contain five of each of the coat proteins. The contours of the outward-facing surfaces of the subunits give to each pentamer the shape of a molecular mountain the VPl subunits, which correspond to the A subunits in T = 3 plant viruses, cluster at the peak of the mountain VP2 and VP3 alternate around the foot and VP4 provides the foundation. The amino termini of the five VP3 subunits of the pentamer intertwine around the fivefold axis in the interior of the virion to form a p stmcture that stabilizes the pentamer and in addition interacts with VP4. 

ATP synthase actually consists of two principal complexes. The spheres observed in electron micrographs make up the Fj unit, which catalyzes ATP synthesis. These Fj spheres are attached to an integral membrane protein aggregate called the Fq unit. Fj consists of five polypeptide chains named a, j3, y, 8, and e, with a subunit stoichiometry ajjSaySe (Table 21.3). Fq consists of three hydrophobic subunits denoted by a, b, and c, with an apparent stoichiometry of ajbgCg.ig- Fq forms the transmembrane pore or channel through which protons move to drive ATP synthesis. The a, j3, y, 8, and e subunits of Fj contain 510, 482, 272, 146, and 50 amino acids, respectively, with a total molecular mass... 

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