Runcong Ke

Electric charge balance mechanism of extended soluble proteins

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.

Human Genome Encodes Many Proteins with Charge Periodicity of 28 Residues

The human genome includes more than 36,000 open reading frames that are translated to amino acid sequences of proteins. When the charge distribution in amino acid sequences from the total human genome was analyzed by the autocorrelation function, a surprisingly sharp periodicity of 28 residues was observed. Every protein with the charge periodicity of 28 residues (PCP28) could be discriminated by a simple algorithm, and the number of PCP28 amounted to about 3% of the total open reading frames of the human genome. The net charge of most PCP28 was highly positive. The possible structural and functional features of this type of protein were discussed in terms of the electric repulsion within molecules.

Ratio of membrane proteins in total proteomes of prokaryota

The numbers of membrane proteins in the current genomes of various organisms provide an important clue about how the protein world has evolved from the aspect of membrane proteins. Numbers of membrane proteins were estimated by analyzing the total proteomes of 248 prokaryota, using the SOSUI system for membrane proteins (Hirokawa et al., Bioinformatics, 1998) and SOSUI-signal for signal peptides (Gomi et al., CBIJ, 2004). The results showed that the ratio of membrane proteins to total proteins in these proteomes was almost constant: 0.228. When amino acid sequences were randomized, setting the probability of occurrence of all amino acids to 5%, the membrane protein/total protein ratio decreased to about 0.085. However, when the same simulation was carried out, but using the amino acid composition of the above proteomes, this ratio was 0.218, which is nearly the same as that of the real proteomic systems. This fact is consistent with the birth, death and innovation (BDI) model for membrane proteins, in which transmembrane segments emerge and disappear in accordance with random mutation events.

Vertebrate genomes code excess proteins with charge periodicity of 28 residues.

All amino acid sequences derived from 248 prokaryotic genomes, 10 invertebrate genomes (plants and fungi) and 10 vertebrate genomes were analysed by the autocorrelation function of charge sequences. The analysis of the total amino acid sequences derived from the 268 biological genomes showed that a significant periodicity of 28 residues is observable for the vertebrate genomes, but not for the other genomes. When proteins with a charge periodicity of 28 residues (PCP28) were selected from the total proteomes, we found that PCP28 in fact exists in all proteomes, but the number of PCP28 is much larger for the vertebrate proteomes than for the other proteomes. Although excess PCP28 in the vertebrate proteomes are only poorly characterized, a detailed inspection of the databases suggests that most excess PCP28 are nuclear proteins.

Local repulsion in protein structures as revealed by a charge distribution analysis of all amino acid sequences from the Saccharomyces cerevisiae genome

The structures and physical properties of individual protein molecules have been extensively studied, but the general features of all proteins in a cell have hardly been investigated. The distribution of net electric charges of all proteins from the Saccharomyces cerevisiae proteome agreed well with a Gaussian distribution. The shift in charge distribution caused by protonation of histidine suggested that the proteins in a cell are buffered against pH changes. A comparison between the amino acid sequences from the proteome and randomly generated sequences indicated that electric charges in the real sequences are clustered. Analysis of autocorrelation function of charged residues in the total proteome of S. cerevisiae showed a positive correlation of net charges in amino acid sequences with characteristic length as long as 81 residues, leading to the conclusion that the interactions within proteins is repulsive on average.