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. 2005 Jan;14(1):74-80.
doi: 10.1110/ps.04984505. Epub 2004 Dec 2.

Electric charge balance mechanism of extended soluble proteins

Nobuyuki Uchikoga  1 , Shun-Ya Takahashi, Runcong Ke, Masashi Sonoyama, Shigeki Mitaku
Affiliations

Electric charge balance mechanism of extended soluble proteins

Nobuyuki Uchikoga et al. Protein Sci. 2005 Jan.

Abstract

Extended proteins such as calmodulin and troponin C have two globular terminal domains linked by a central region that is exposed to water and often acts as a function-regulating element. The mechanisms that stabilize the tertiary structure of extended proteins appear to differ greatly from those of globular proteins. Identifying such differences in physical properties of amino acid sequences between extended proteins and globular proteins can provide clues useful for identification of extended proteins from complete genomes including orphan sequences. In the present study, we examined the structure and amino acid sequence of extended proteins. We found that extended proteins have a large net electric charge, high charge density, and an even balance of charge between the terminal domains, indicating that electrostatic interaction is a dominant factor in stabilization of extended proteins. Additionally, the central domain exposed to water contained many amphiphilic residues. Extended proteins can be identified from these physical properties of the tertiary structure, which can be deduced from the amino acid sequence. Analysis of physical properties of amino acid sequences can provide clues to the mechanism of protein folding. Also, structural changes in extended proteins may be caused by formation of molecular complexes. Long-range effects of electrostatic interactions also appear to play important roles in structural changes of extended proteins.

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Figures

Figure 1.
Figure 1.
(A) Schematic model of dumbbell-type (extended) protein; WNN=WCC=1. (B) Dispersion diagram of WCC vs. WNN for selection of dumbbell-type proteins based on the criterion WNN=WCC=1.
Figure 2.
Figure 2.
(A) Distribution of net charge, from single structural data in PDB. (B) Distribution of charge density. (C) Charge balance of N- and C-terminal halves.
Figure 3.
Figure 3.
(A) Relative amino acid propensity of termini and central region of central helices of 11 extended proteins normalized by propensity in globular domains. If a value of relative propensity was greater than unity in a region, correspondent residues appeared frequently in that region. Helix termini were defined as the eight residues shown in Fig. 3B (two shaded regions). The remaining region of the helix was designated the central region. (B) Example of hydropathy and amphiphilicity plot of calmodulin (1OSA). The average value of every seven residues in each sequence was plotted as a function of sequence number. Solid line indicates hydrophobicity, using the K-D index (Kyte and Doolittle 1982). Dotted line indicates amphiphilicity, using the index developed by Mitaku et al. (2002). Amphiphilicity index: K, 3.67; R, 2.45; H, 1.45; E, 1.27; Q, 1.25.
Figure 4.
Figure 4.
SOSUIdumbbell Web site: http://bp.nuap.nagoya-u.ac.jp/sosui/sosuidumbbell/dumbbell_submit.html. This Web site can be used to determine whether a query sequence is an extended protein. If the query sequence is predicted to be an extended protein, the results page shows the central helical component exposed to water.
Figure 5.
Figure 5.
Two possible structures of extended proteins in bound state. The unbound extended protein molecule forms a stable extended structure with electrostatic repulsion between the terminal domains (middle left). When the extended protein binds to a globular molecule, interaction between the terminals of the extended protein weakens, causing it to collapse (bottom left). When the extended protein binds to an extended molecule, it remains in an extended structure (bottom right).
See this image and copyright information in PMC

References

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