Multimeric protein

The terms polypeptide and protein are used interchangeably in discussing single polypeptide chains. The term protein broadly defines molecules composed of one or more polypeptide chains. Proteins having only one polypeptide chain are monomeric proteins. Proteins composed of more than one polypeptide chain are multimeric proteins. Multimeric proteins may contain only one kind of polypeptide, in which case they are homomultimeric, or they may be composed of several different kinds of polypeptide chains, in which instance they are heteromultimeric. Greek letters and subscripts are used to denote the polypeptide composition of multimeric proteins. Thus, an ag type protein is a dimer of identical polypeptide subunits, or a homodimer. Hemoglobin (Table 5.1) consists of four polypeptides of two different kinds it is an hetero-multimer. 

If the protein of interest is a heteromultimer (composed of more than one type of polypeptide chain), then the protein must be dissociated and its component polypeptide subunits must be separated from one another and sequenced individually. Subunit associations in multimeric proteins are typically maintained solely by noncovalent forces, and therefore most multimeric proteins can usually be dissociated by exposure to pEI extremes, 8 M urea, 6 M guanidinium hydrochloride, or high salt concentrations. (All of these treatments disrupt polar interactions such as hydrogen bonds both within the protein molecule and between the protein and the aqueous solvent.) Once dissociated, the individual polypeptides can be isolated from one another on the basis of differences in size and/or charge. Occasionally, heteromultimers are linked together by interchain S—S bridges. In such instances, these cross-links must be cleaved prior to dissociation and isolation of the individual chains. The methods described under step 2 are applicable for this purpose. 

When two or more distinct peptide chains are involved, the nature of their interactions can be quite complicated. Multimeric proteins with more than one kind of subunit often display different affinities between different pairs of sub-... 

The quaternary structure - the spatial relationship between the protein chains in a multimeric protein. 

Hemoglobins bind four molecules of Oj per tetramer, one per heme. A molecule of Oj binds to a hemoglobin tetramer more readily if other Oj molecules are already bound (Figure 6-4). Termed cooperative binding, this phenomenon permits hemoglobin to maximize both the quantity of O2 loaded at the PO2 of the lungs and the quantity of O2 released at the PO2 of the peripheral tissues. Gooperative interactions, an exclusive property of multimeric proteins, are critically important to aerobic life. 

Plant-based production systems are now being used commercially for the synthesis of foreign proteins [1-3]. Post-translational modification in plant cells is similar to that carried out by animal cells plant cells are also able to fold multimeric proteins correctly. The sites of glycosylation on plant-produced mammalian proteins are the same as on the native protein however, processing of N-linked glycans in the secretory pathway of plant cells results in a more diverse array of glycoforms than is produced in animal expression systems [4]. Glycoprotein activity is retained in plant-derived mammalian proteins. 

The folding of polypeptide chains and the assembly of multiple subunits are critical requirements when complex and multimeric proteins such as full size antibodies... 

The ability to stack genes in transgenic plants by successive crosses between individually transformed parental plants is a considerable advantage in attempting to construct multimeric protein complexes, such as secretory antibodies. As described earher, slgA consists of two basic Ig monomeric units (heavy and tight chains) that are dimerized by a joining (J) chain and then associated with a fourth polypeptide, the secretory component (SC) [36]. 

Enz, R. and Croci, C. (2003) Different binding motifs in the metabotropic glutamate receptor type 7b for filamin-A, PP1C, PICK1 and syntenin allow the formation of multimeric protein complexes. Biochem. J. 372,183-191. 

Powell, K.D. Wales, T.E. Fitzgerald, M.C. Thermodynamic stability measurements on multimeric proteins using a new H/D exchange-and matrix-assisted laser desorption/ ionization (MALDl) mass spectrometry-based method. Protein Sci. 2002, 11, 841-851. 

The coding sequences of a- and P-globins of human hemoglobin have been fused to the sequence of the chloroplastic transit peptide of the small subunit of Rubisco. These proteins were then coexpressed in transgenic tobacco plants, resulting in the production of a functional form of tetra-meric hemoglobin. The results demonstrate that a complex multimeric protein such as recombinant human hemoglobin can be obtained from tobacco in a functional form. 

A multisubunit protein is also referred to as a mul-timer. Multimeric proteins can have from two to hundreds of subunits. A multimer with just a few subunits... 

Identical subunits of multimeric proteins are generally arranged in one or a limited set of symmetric patterns. A description of the structure of these proteins requires an understanding of conventions used to define symmetries. Oligomers can have either rotational symmetry or helical symmetry that is, individual subunits can be superimposed on others (brought to coincidence) by rotation about one or more rotational axes, or by a helical rotation. In proteins with rotational symmetry, the subunits pack about the rotational axes to form closed structures. Proteins with helical symme-... 

Quaternary structure results from interactions between the subunits of multisubunit (multimeric) proteins or large protein assemblies. Some multimeric proteins have a repeated unit consisting of a single subunit or a group of subunits referred to as a protomer. Protomers are usually related by rotational or helical symmetry. 

Cooperative binding of a ligand to a multimeric protein, such as we observe with the binding of 02 to hemoglobin, is a form of allosteric binding often observed in multimeric proteins. The binding of one ligand affects... 

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