Oligomeric protein assembly

Hemmingsen, S. M., C. Woolford, S. M. van der Vies, K. Tilly, D. T. Dennis, C. P. Georgopoulos, R. W. Hendrix, and R. J. Ellis (1988). Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature333, 330-334. 

Hemmingsen SM, Woolford C, van de Vies SM, Tilly K, Dennis DT, Georgopoulos CP, Hendrix RW, Ellis RJ (1988) Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature 33 330-334 Hendrick JP, Haiti F-U (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62 349-384... 

Quaternary structure the four separate chains Of hemoglobin assembled S3 into an oligomeric protein... 

Caspar and Klug (1962) made an important distinction between two fundamental types of assembly processes. True self-assembly was conceptualized as a series of reactions relying on the propensity of subunits to condense and form assembled structures strictly as a result of the information encoded in the architecture of the components. On the other hand, template-directed assembly may be considered as a process depending on the presence of a separate template that imparts structural constraints on the pathway for constructing the final assembled structure. True self-assembly is observed, for example, in the formation of many oligomeric proteins. Indeed, Friedman and Beychok (1979) have re-... 

Quaternary structure. Due to non-covalent interactions, many proteins assemble to form symmetrical complexes (oligomers). The individual components of oligomeric proteins (usually 2-12) are termed subunits or monomers. Insulin also forms quaternary structures. In the blood, it is partly present as a dimer. In addition, there are also hexamers stabilized by Zn ions (light blue) (3), which represent the form in which insulin is stored in the pancreas (see p.l60). 

True self-assembly is observed in the formation of many oligomeric proteins. Indeed, Friedman and Beychok reviewed efforts to define the subunit assembly and reconstitution pathways in multisubunit proteins, and all of the several dozen examples cited in their review represent true self-assembly. Polymeric species are also formed by true self-assembly, and the G-actin to F-actin transition is an excellent example. By contrast, there are strong indications that ribosomal RNA species play a central role in specifying the pathway to and the structure of ribosome particles. And it is interesting to note that the assembly of the tobacco mosaic virus (TMV) appears to be a two-step hybrid mechanism the coat protein subunits first combine to form 34-subunit disks by true self-assembly from monomeric and trimeric com-... 

Figure 5.6 Self-organization in oligomeric proteins. (A) The transacetylase core of the pyruvate dehydrogenase complex. The core consists of 24 identical chains (12 can be seen in this view). (B) The aspartate transcarbamoylase, formed by six catalytic (lighter subunits) and six regulatory chains (darker subunits) (Bi) view showing the threefold symmetry (B2) a perpendicular view. (C) The helical assembly of several identical globular subunits in F-actin polymer. The helix repeats after 13 subunits. (All adapted from Stryer, 1975.)...

Just as the amino acids, sugars, and nucleotides are the building blocks for formation of proteins, polysaccharides, and nucleic acids, these three kinds of macromolecule are the units from which larger subcellular structures are assembled. Fibers, microtubules, virus "coats," and small symmetric groups of subunits in oligomeric proteins all result from the packing of macromolecules in well-defined ways, something that is often called quaternary structure. 

While it is easy to visualize the assembly of oligomeric proteins, it is not as easy to imagine how complex objects such as eukaryotic cilia (Fig. 1-8) or the sarcomeres of muscle (Fig. 19-6) are formed. However, study of the assembly of bacteriophage particles and other small biological objects has led to the concepts of self-assembly and assembly pathways, concepts that are now applied to every aspect of the architecture of cells. 

Monomeric intermediates during the assembly of oligomeric proteins are usually inactive and the formation of native quaternary structures are often a prerequisite for catalytic activity. One clear reason for this is that the active sites of some enzymes are located at the interface between subunits and are formed by amino acid residues from different subunits. Such examples are aspartate transcarbamoylase from K coli5) and ribulose bisphosphate carboxylase/oxygenase from Rhodospirillum rubrum.6)... 

The members of the 70-kDa heat shock protein (hspVO) family perform functions that are essential for cell viability, both under normal and stress conditions. Constitutively expressed hsp70s are thought to be involved in the folding and assembly of newly synthesized proteins, disassembly of oligomeric proteins, protein degradation, and the transport of nascent peptide chains across membranes (l, 2). 

Recruitment of the initiator procaspases into a multiprotein complex results from a regulated series of protein-protein interactions mediated by interaction modules . Four types of interaction modules are involved in the activation of initiator caspases and thus play important roles in the initiation of apoptosis (review Weber and Vin-cenz, 2001). These domains have been named the death domain (DD),, the death effector domain (DED), the caspase activation and recruitment domain (CARD), and the less characterized pyrin domain. The domains are found on several components of the apoptotic signaling pathways and mediate homotypic protein-protein interactions, i. e., a given module will interact only with a member of the same family and not with members of the other families. Since members of the same module are found on different proteins, these modules mediate the assembly of hetero-oligomeric protein complexes. As examples, DDs are found on death receptors and their cofactors, D EDs on cofactors and the initiator caspase-8, and CARDS on cofactors, caspase-2, and caspase-9. 

Reddy, P. S., and Corley, R. B. (1998). Assembly, sorting and exit of oligomeric proteins from the endoplasmic reticulum. Bioessays 20, 546-554. 

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