Latent Periodicity of Serine/Threonine and Tyrosine Protein Kinases and Other Protein Families

A method of noise decomposition has been developed. This method allows for the identification of a latent periodicity with symbol insertions and deletions that is specific for all or most amino acid sequences belonging to the same protein family or protein domain. The latent periodicity has been identified in catalytic domains of 85% of serine/threonine and tyrosine protein kinases. Similar results have been obtained for 22 other protein families. The possible role of latent periodicity in protein families is discussed.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 3, 2005, pp. 420–436.Original Russian Text Copyright © 2005 by Laskin, Kudryashov, Skryabin, Korotkov.     

Developing a mathematical method to search for latent periodicity in protein amino-acid sequences with deletions and insertions

A mathematical method has been developed in order to search for latent periodicity in protein amino-acid and other symbolical sequences using dynamic programming and random matrices. The method allows the detection of the latent periodicity with insertions and deletions at positions that are unknown beforehand. The developed method has been applied to search for the periodicity in the amino-acid sequences of several proteins and in the euro/dollar exchange rate since 2001. The presence of a long period with insertions and deletions in amino-acid sequences is shown. The period length of seven amino acids is observed in the proteins that contain supercoiled regions (a coiled-coil structure) as well as of six, five, or more amino acids. The existence of the period length of 6 and 7 days, as well as 24 and 25 h in the analyzed financial time series is observed; note that this periodicity is detectable only for insertions and deletions. The causes that underlie the occurrence of the latent periodicity with insertions and deletions in amino-acid sequences and financial time series are discussed.     

Identification of latent periodicity in amino acid sequences of protein families

For detection of the latent periodicity of the protein families responsible for various biological functions, methods of information decomposition, cyclic profile alignment, and the method of noise decomposition have been used. The latent periodicity, being specific to a particular family, is recognized in 94 of 110 analyzed protein families. Family specific periodicity was found for more than 70% of amino acid sequences in each of these families. Based on such sequences the characteristic profile of the latent periodicity has been deduced for each family. Possible relationship between the recognized latent periodicity, evolution of proteins, and their structural organization is discussed.     

Method revealing latent periodicity of the nucleotide sequences modified for a case of small samples.

An earlier reported method for revealing latent periodicity of the nucleotide sequences has been considerably modified in a case of small samples, by applying a Monte Carlo method. This improved method has been used to search for the latent periodicity of some nucleotide sequences of the EMBL data bank. The existence of the nucleotide sequences' latent periodicity has been shown for some genes. The results obtained have implied that periodicity of gene structure is projected onto the periodicity of primary amino acid sequences and, further, onto spatial protein conformation. Even though the periodic structure of gene sequences has been eroded, it is still retained in primary and/or spatial structures of corresponding proteins. Furthermore, in a few cases the study of genes' periodicity has suggested their possible evolutionary origin by multifold duplications of some gene's fragments.     

Latent sequence periodicity of some oncogenes and DNA-binding protein genes

A method of latent periodicity search is developed. We use mutualinformation to reveal the latent periodicity of mRNA sequences.The latent periodicity of an mRNA sequence is a periodicitywith a low level of similarity between any two periods insidethe mRNA sequence. The mutual information between an artificialnumerical sequence and an mRNA sequence is calculated. The lengthof the artificial sequence period is varied from 2 to 150. Thehigh level of the mutual information between artificial andmRNA sequences allows us to find any type of latent periodicityof mRNA sequence. The latent periodicity of many mRNA codingregions has been found. For example, the retinoblastoma geneof HSRBS clone contains a region with a latent period equalto 45 bases. The A-RAF oncogene of HSARAFIR clone contains aregion with a latent period equal to 84 bases. Integrated sequencesfor the regions with latent periodicity are determined. Thepotential significance of latent periodicity is discussed.     

Identification of latent periodicity in domains of alkaline proteases

Internal repeats in protein sequences have wide-ranging implications for the structure and function of proteins. A keen analysis of the repeats in protein sequences may help us to better understand the structural organization of proteins and their evolutionary relations. In this paper, a mathematical method for searching for latent periodicity in protein sequences is developed. Using this method, we identified simple sequence repeats in the alkaline proteases and found that the sequences could show the same periodicity as their tertiary structures. This result may help us to reduce difficulties in the study of the relationship between sequences and their structures.     

Latent periodicity of protein families, identified with the indel-aware algorithm

Latent amino acid repeats seem to be widespread in genetic sequences and to reflect their structure, function, and evolution. We have recently identified latent periodicity in more than 150 protein families including protein kinases and various nucleotide-binding proteins. The latent repeats in these families were correlated to their structure and evolution. However, a majority of known protein families were not identified with our latent periodicity search algorithm. The main presumable reason for this was the inability of our techniques to identify periodicities interspersed with insertions and deletions. We designed the new latent periodicity search algorithm, which is capable of taking into account insertions and deletions. As a result, we identified many novel cases of latent periodicity peculiar to protein families. Possible origins of the periodic structure of these families are discussed. Summarizing, we presume that latent periodicity is present in a substantial portion of known protein families. The latent periodicity matrices and the results of Swiss-Prot scans are available from http://bioinf.narod.ru/del/.     

The informational concept of searching for periodicity in symbol sequences

Method of informational decomposition has been developed, allowing one to reveal hidden periodicity in any symbol sequences. The informational decomposition is calculated without conversion of a symbol sequence into the numerical one, which facilitates finding periodicities in a symbol sequence. The method permits introducing an analog of the autocorrelation function of a symbol sequence. The method developed by us has been applied to reveal hidden periodicities in nucleotide and amino acid sequences, as well as in different poetical texts. Hidden periodicity has been detected in various genes, testifying to their quantum structure. The functional and structural role of hidden periodicity is discussed.     

Investigation of periodic distributions of amino acids in the sequences of fiber proteins of bacteriophage T4

Sequences of amino acids of some fiber proteins may have a periodic structure. To analyze this periodicity Fourier transform of a mathematical image of symbolic sequence of amino acids in a protein is sometimes used. In this work we employed one (out of few possible) particular way of doing Fourier transform as the most straightforward and optimal. Employing this optimal Fourier transform method we analyzed periodicity of fiber proteins in bacteriophage T4. As a result we managed to confirm that a certain periodicity exists in the investigated proteins. It was found that for a number of proteins the alternation of elements of the same group in the amino acid sequence with a rather small period T = 15 exists, whereas for some other proteins alternations have small periods 10 and 8. The new result is a discovery of relatively large periods of amino acids alternations, which divide the amino acids sequence of the protein into 4 or 6 equal parts. These data on the amino acids periodicity allowed us to align amino acids sequences in accordance with the established periods of both types, in agreement with certain results obtained in X-ray crystallography and electron microscopy experiments.     

The Informational Concept of Searching for Periodicity in Symbol Sequences

A method of informational decomposition has been developed, allowing one to reveal hidden periodicity in any symbol sequence. The informational decomposition is calculated without conversion of a symbol sequence into a numerical one, which facilitates finding periodicities in a symbol sequence. The method permits introducing an analog of the autocorrelation function of a symbol sequence. The method developed by us has been applied to reveal hidden periodicities in nucleotide and amino acid sequences, as well as in different poetical texts. Hidden periodicity has been detected in various genes, testifying to their quantum structure. The functional and structural role of hidden periodicity is discussed.     

Study of the periodic arrangement of amino acid residues in fiber proteins of bacteriophage T4

The amino acid sequences of some fiber proteins possibly have a periodic structure. This periodicity can be analyzed using the Fourier transform of the mathematical image of the symbol sequence of amino acid residues in proteins. One of several possible methods of Fourier transform has been chosen as optimal for the given study. This optimal Fourier transform has been used to analyze the periodic structures in several fiber proteins of bacteriophage T4. Amino acids from some groups form sequences of alternating elements with a relatively small period (T=15); those from other groups form sequences with other small periods (T=10 and T=8). Relatively large periods of amino acid arrangement, with the entire amino acid sequence of the protein being divided between them into four or six equal parts, is a new finding. The data on protein structural periodicity make it possible to align the amino acid sequences according to the periodic structures of both type. The results obtained agree with the results of previous crystallographic and electron microscopic studies.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 321–329.Original Russian Text Copyright © 2005 by Simakova, Simakov.     

Genome analysis of MG virus, a human papovavirus.

The single late 26S mRNA of Semliki Forest virus (SFV) directs the synthesis of the four viral structural proteins, C, E3, E2, and E1, and the recently described nonstructural protein, 6K. We report here partial NH2-terminal amino acid sequences of the SFV polypeptides E3 and 6K and of p62, the precursor to E3 and E2. In addition, were have determined a partial NH2-terminal sequence of the Sindbis virus homolog of 6K, the 4.2K protein. p62 and E3 of SFV have identical NH2-terminal amino acid sequences. Comparison of the partial NH2-terminal sequences of 6K of SFV and 4.2K of Sindbis virus with the deduced amino acid sequence encoded by the 26S mRNA of each virus reveals that the genes for these peptides are located in each case between those for E2 and E1. The order of the genes on the 26S mRNA of the alphaviruses is therefore 5'-C-E3-E2-6K-E1-3'. We discuss two mechanisms by which the nascent viral glycoproteins may be inserted into the membrane of the endoplasmic reticulum.     

The structural periodicity ofE. coli ribosomal proteins

It is established that the sequences of all different proteins fromE. coli ribosome as well as two protein biosynthesis initiation factors, two ribosome-associated DNA-binding proteins, and the elongation factor EF-Tu from the same source possess a periodicity expressed more weakly and different from that found earlier for a number of proteins representatives of 18 superfamilies. The statistical significance of the periodicity observed was checked by comparing the area below the periodicity curve of every protein examined with that of computer generated sequences having the same amino acid composition and length. The results concerning the proteins from small and large ribosomal subunit are compared. The conclusions support and supplement the concept about the presence of a trend in protein molecular evolution from universal (Gly, Ala) to specialized (Phe, Tyr, Trp, Cys) amino acids.     

Bovine heart mitochondrial F6: HPLC purification, NH2-terminal sequence and the possible structural relatedness to other components of ATPase complexes

The mitochondrial factor F6 has been purified by reverse-phase HPLC and the molecular weight (8500), amino acid composition and about 25% of the amino acid sequence determined. In the NH2-terminal sequence of the first 18 amino acids (NKELDPVQKLFVDKIREY), six identities with the NH2-terminal sequence of the oligomycin-sensitivity conferring protein (OSCP) are apparent, as well as less striking similarities with the OSCP related subunit delta of E. coli F1. The possibility that F6, OSCP and subunit delta of E. coli F1 could have evolved from a common ancestral gene is supported by apparent gene duplication within the OSCP and subunit delta sequences.     

Hexapeptide repeat structure in Dictyostelium spore coat protein

The sequences of the NH2-termini of two spore coat proteins of Dictyostelium discoideum have been determined. One of them (SP60) consists of perfect hexapeptide repeats of the sequence Gly-Asp-Trp-Asn-Asn-Asx-. The sequence has some homology to the parvovirus capsid protein which does not display periodicity. The NH2-terminal sequence of the second protein, SP70, contains a modified amino acid in two positions and like SP60 is highly hydrophilic and acidic.     

Genetic organization of the KpnI restriction--modification system.

The KpnI restriction-modification (KpnI RM) system was previously cloned and expressed in E. coli. The nucleotide sequences of the KpnI endonuclease (R.KpnI) and methylase (M. KpnI) genes have now been determined. The sequence of the amino acid residues predicted from the endonuclease gene DNA sequence and the sequence of the first 12 NH2-terminal amino acids determined from the purified endonuclease protein were identical. The kpnIR gene specifies a protein of 218 amino acids (MW: 25,115), while the kpnIM gene codes for a protein of 417 amino acids (MW: 47,582). The two genes transcribe divergently with a intergeneic region of 167 nucleotides containing the putative promoter regions for both genes. No protein sequence similarity was detected between R.KpnI and M.KpnI. Comparison of the amino acid sequence of M.KpnI with sequences of various methylases revealed a significant homology to N6-adenine methylases, a partial homology to N4-cytosine methylases, and no homology to C5-methylases.     

枯草芽孢杆菌渗透压调节基因proB的克隆和表达

用PCR扩增的方法从耐盐的枯草杆菌中克隆出一个13kb长的DNA片段,经功能检测,证明正向插入片段与大肠杆菌的脯氨酸营养缺陷特性(proB-)能够营养互补。含有该重组质粒的大肠杆菌DH5α在基本培养基上的耐盐能力从2%提高至4%。通过引物步行法测定了该插入片段的核苷酸序列。利用DNAsis软件进行序列分析发现,该片段第122～1235bp核苷酸编码一个由370个氨基酸组成的蛋白质分子,其上游存在非典型的-10区,典型的-35区和核糖体结合位点,起始密码子处有最佳翻译起始效率的侧翼核苷酸序列。将其与Genebank中的已知基因的序列和编码的氨基酸序列进行同源性比较,结果表明该片段与枯草杆菌168的核苷酸序列、氨基酸序列的同源性分别为81%和90%。证明该基因确实是一个proB基因。通过与三十个不同种属微芽生物proB基因的氨基酸序列比较,发现该蛋白存在有可能与形成酶的活性中心和三维结构有密切关系的几个绝对保守的区域。     

Primary structure of protein S13 from the small subunit of escherichia coli ribosomes.

The experimental details which led to the determination of the complete primary structure of protein S13 from the small subunit of Escherichia coli ribosomes are presented. S13 consists of 117 amino acid residues and has the following composition: Asp6, Asn2, Thr6, Ser6, Glu6, Gln2, Pro4, Gly11, Ala11, Cys1, Val7, Met2, Ile12, Leu9, Tyr2, Phe1, His3, Lys11 and Arg15. Tryptophan was not found. The molecular weight of protein S13 as derived from the sequence shown in Fig. 1 is 12970. The amino acid sequence of the protein was determined by combining the results obtained from liquid phase Edman degradation of the intact protein with those from the peptides isolated after enzymatic digestions with trypsin, Staphylococcus aureus protease and thermolysin. Additional information about the primary structure was derived from analysis of the chymotryptic peptides of protein S13 and from its digestion with carboxypeptidase C. The amino acid sequence of protein S13 was compared with the published sequences of the other ribosomal proteins of E. coli and predictions for the secondary structure of this protein were made.     

The complete primary structure of the human snRNP E protein.

The snRNP E protein is one of four "core" proteins associated with the snRNAs of the U family (U1,U2,U4,U5, and U6). Screening of a human teratoma cDNA library with a partial cDNA for a human autoimmune antigen resulted in the isolation of a cDNA clone containing the entire coding region of this snRNP core protein. Comparison of the 5' end of this cDNA with the sequences of two processed pseudogenes and primer extension data suggest that the cDNA is nearly full length. The longest open reading frame in this clone codes for a basic 92 amino acid protein which is in perfect agreement with amino acid sequence data obtained from purified E protein. The predicted sequence of this protein reveals no extensive similarity to other snRNP proteins, but contains regions of similarity to a eukaryotic ribosomal protein.