Folding units

Gegg, C. V., Bowers, K. E., and Matthews, C. R. (1997). Probing minimal independent folding units in dihydrofolate reductase by molecular dissection. Protein Sci. 6, 1885-1892. 

Domains have proved so fruitful in explaining both the structure and the function of proteins that the concept is certain to survive in one form or another. At some time in the near future it will presumably acquire full scientific respectability with a verifiable definition in terms of either folding units or genetic units or perhaps both. 

The most characteristic features of this proposed folding scheme are the proposal of different kinds of nucleation for the different major structure types, the postulation of some rather large-scale concerted folding units, and the prediction of folding intermediates with somewhat greater amounts of the same sort of secondary structure found in the final native protein. The last effect might turn out to be most pronounced in those proteins with very irregular secondary structures. 

The resolution as adjusted by the U/V ratio cannot arbitrarily be increased, but is ultimately limited by the mechanical accuracy with which the rods are constructed and supported ( 10pm). [Ill] Above an m/z value characteristic of each quadrupole assembly, any further improvement of resolution can only be achieved at the cost of significantly reduced transmission. High-performance quadrupoles allowing for about 10-fold unit resolution have only recently been developed. [112]... 

With external ion sources it became feasible to interface any ionization method to the QIT mass analyzer. [171] However, commercial QITs are chiefly offered for two fields of applications i) GC-MS systems with El and Cl, because they are either inexpensive or capable of MS/MS to improve selectivity of the analysis (Chap. 12) and ii) instruments equipped with atmospheric pressure ionization (API) methods (Chap. 11) offering higher mass range, and some 5-fold unit resolution to resolve isotopic patterns of multiply charged ions (Fig. 4.47). [149,162,172,173]... 

Domain A region of a protein, often forming a self-contained folded unit. 

Perczel, A., Jakli, I., Csizmadia, I.G. (2003). Intrinsically stable secondary structure elements of proteins A comprehensive study of folding units of proteins by computation and by analysis of data determined by x-ray crystallography. Chemistry, 9(21), 5332-5342. 

Kammerer, R. A., Schulthess, T., Landwehr, R., Lustig, A., Engel, J., Aebi, U., and Steinmetz, M. O. (1998). An autonomous folding unit mediates the assembly of two-stranded coiled coils. Proc. Natl. Acad. Sci. 95, 13419-13424. 

Cooperative folding units are defined from a functional rather than a purely structural point of view, even though in many cases a one-to-one correspondence can be found. Cooperative folding units can be as large as the entire protein (e.g., small globular proteins that exhibit two-state behavior effectively behave as cooperative folding units), entire protein domains, subdomains, and structural motifs, or as small as single a helices. The hierarchical level at which the description is made depends on the desired level of detail and is, in principle, only constrained by the availability of structural information. 

According to the hierarchical approach, the number of states that need to be considered in the partition function is 2"cu, where ncu is the number of cooperative folding units. In order to develop a complete description of a system composed of ncu interacting cooperative folding units it is necessary to evaluate the intrinsic energetics of each... 

Fig. 6. Representation of states for a hypothetical protein composed of two cooperative folding units. Free energy differences designated in uppercase letters represent the intrinsic stabilities of the cooperative units and have a contribution to the statistical weights designated by k. Free energy differences designated in lowercase letters represent the interaction between cooperative units and have a contribution to the statistical weights designated by . [Reprinted from Freire and Murphy (1991).]...

An a-helix bundle may become a second-order cooperative folding unit if the interaction energy terms are such that the intermediate terms in the partition function become negligibly small [Eq. (14)] and the entire partition function reduces to a two-state partition function (i.e., a partition function of the form 1 + e G/RT). If such is the case, the a-helix bundle will be either completely folded or unfolded. Higher order cooperative folding units can be constructed from lower order ones following the same rules. The most immediate application of this approach is to proteins exhibiting pure a-helical structural motifs. 

Wallqvist A, Smythers GW, Covel DG (1997) Identification of cooperative folding units in a set of native proteins, Protein Sci, 6 1627—42... 

Murphy KP, Bhakuni V, Xie D, Freire E (1992) Molecular basis of cooperativity in protein folding. III. Structural identification of cooperative folding units and folding intermediates, J Mol Biol, 227 293-306... 

Fig. 4-11 Diagrammatic representation of the supersecondary fi-a-fi folding unit of a protein, p regions are represented by the arrows, while the a-helical segment is indicated by the coiled structure. Approximate positions of hydrogen bonds are shown with dashed lines.

Larger proteins may fold into separate domains, each domain being a globular folding unit with its own interior and surface, and with an interconnecting strand of backbone linking the domains. 

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