Close structural resemblance between putative polymerase of a Drosophila transposable genetic element 17.6 and pol gene product of Moloney murine leukaemia virus.

Toh, Hiroyuki; Kikuno, Reiko; Hayashida, Hidenori; Miyata, Takashi; Kugimiya, Wataru; Inouye, Satoshi; Yuki, Shunji; Saigo, Kaoru

doi:10.1002/j.1460-2075.1985.tb03771.x

Cited by 158 publications

(95 citation statements)

References 37 publications

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“…Furthermore, underlining labelled g, h and i in Fig. 1 show that, as with 17.6 and 297, ORF2 includes the nucleotide sequences corresponding to the highly conserved amino acid sequences of retroviral protease, reverse transcriptase and integrase [18]. Thus, the genome organization of 412 is essentially the same for the most part as those of other copia-like elements examined so far (Fig.…”

Section: Resultsmentioning

confidence: 76%

Nucleotide sequence characterization of a Drosophila retrotransposon, 412

et al. 1986

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The nucleotide sequence of the internal region of a Drosophila retrotransposon. 412, was determined. The genome of 412 was found to consist of two long open-reading frames (ORFs 1 and 2), an unusually long putative leader region and long terminal repeats (LTRs). As with 17.6, 297 and gypsy, ORFs 1 and 2 slightly overlap each other and are out of phase by + 2 . ORF2 includes the nucleotide sequences coding for the putative protease, reverse transcriptase and integrase, and is similar in entire organization to the pol gene of Moloney murine leukaemia virus. In spite of the difference in insertion specificity, integrase, an enzyme presumably responsible for insertion, was found to be similar in amino acid sequence to the counterparts of 17.6, 297 and gypsy. There is no ORF in 412 which corresponds to retroviral env or ORF3s of 17.6 and 297. Analysis of 412 transcripts suggested that 412 LTR is composed of U3, R and U5. The gene for a potential primer tRNA for putative reverse transcription of 412 was also surveyed and the 3'-terminal 15 nucleotides of a putative arginine tRNA were found to be exactly complementary to the putative primer-binding site of 412.Drosophila copia-like elements or retrotransposons are formed from the largest group of transposable genetic elements in Drosophila melanogaster. They are intimately related in evolution to retroviral proviruses in vertebrates In our previous experiments the complete nucleotide sequences of three Drosophila retrotransposons 17.6 [15], 297 [16] and copia [17] were determined. 17.6 and 297 contained three open reading frames (ORFs) similar in size and location to retroviral gag, pol and env. The second ORFs of these two elements were further shown each to include the nucleotide sequence coding for a reverse-transcriptase-like enzyme and be, in all respects of their organization, very similar to the pol gene of Moloney murine leukaemia virus (Mo-MuLV) [15,16, 181. In contrast, the genome of copia contained a single long ORF [17, 191 including genes for the major capsid protein of copia-related virus-like particles and reverse-transcriptase-like enzyme much less similar to the reverse transcriptase of MoMuLV [17,19]. These results suggest the genome organization in Drosophila retrotransposons to be very much diversified.To confirm and determine the further implications of this notion, a determination was made of the complete nucleotide sequence of another Drosophila retrotransposon, 412, having terminal dinucleotides identical to those of copia and retrovirus proviruses but different from those of 17.6, 297 and gypsy [4, 15-17, 20, 211. The genome of 412 was found to contain two long ORFs (ORFs 1 and 2) and an unusually long putative leader region with two short ORFs. As with 17.6 [15], 297 [16] and gypsy (unpublished), ORFs 3 and 2 slightly overlap each other and are out of phase by t 2 . The entire structure of ORF2 is of the 17.6 type and the putative integrase encoded by a portion of ORF2 is similar in amino acid sequence to the counterparts of 17.6, 297 and gy...

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Section: Resultsmentioning

confidence: 76%

Nucleotide sequence characterization of a Drosophila retrotransposon, 412

et al. 1986

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“…In two of the examples, alignments with a low degree of sequence similarity extending over [20][21][22][23][24][25][26][27][28][29][30] residues are found, while in one instance a short but well conserved motif is located that corresponds to an active site. Example 1.…”

Section: Biological Examplesmentioning

confidence: 99%

“…The conserved "DTG" (aspartic acid-threonine-glycine) pattern in this set of retroviral Pol proteins is the active site in aspartyl proteases. A detailed analysis of viral polymerases led to the observation of this pattern (25), yet it is apparent in a single three-way database search. Discussion Existing sequence database search methods have been remarkably effective in detecting biologically significant relationships.…”

Section: Biological Examplesmentioning

confidence: 99%

Protein database searches for multiple alignments.

Altschul

Lipman

1990

Proc. Natl. Acad. Sci. U.S.A.

435

246

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Protein database searches frequently can reveal biologically significant sequence relationships useful in understanding structure and function. Weak but meaningful sequence patterns can be obscured, however, by other similarities due only to chance. By searching a database for multiple as opposed to pairwise alignments, distant relationships are much more easily distinguished from background noise. Recent statistical results permit the power of this approach to be analyzed. Given a typical query sequence, an algorithm described here permits the current protein database to be searched for three-sequence alignments in less than 4 min. Such searches have revealed a variety of subtle relationships that pairwise search methods would be unable to detect.Protein and nucleic acid sequence comparison has become an important tool for molecular biologists. Frequently the first clues to the structure or function of a newly sequenced protein come from similarities it exhibits to other proteins that have already been studied. Protein database searches can draw the researcher's attention to unsuspected relationships and suggest future lines for investigation (1,2). One problem is that while close relationships are easy to discover with existing tools, weaker ones may be indistinguishable from chance similarities that would be found between even random sequences. As the size of the protein database increases, the "noise" from chance similarities found in database searches grows as well, making weak relationships ever harder to detect.One strategy for distinguishing a chance sequence pattern from a biologically relevant one is to search the database for several instances of it among otherwise dissimilar proteins. The basic principle is that while an unusual event may be due to chance, recurrence ofthe same event requires explanation: lightning striking twice in the same place probably indicates a lightning rod. In this paper, we discuss how recent statistical results (3, 4) allow us to clothe this intuition in numbers, so that a multiple alignment is seen to be statistically significant while none of the pairwise alignments that comprise it are. We also describe a simple computational strategy that allows a database to be searched for multiple alignments in reasonable time. This approach is distinct from "profile analysis" (5) and related methods (6-8), which search for pairwise similarities to a sequence "profile" derived from a predefined multiple alignment. In contrast, our method takes a single query sequence and searches a standard database of individual protein sequences for segments with which it can form statistically significant multiple alignments. An obvious generalization would be to use a profile as the query. Using our method to search the National Biomedical Research Foundation Protein Identification Resource (PIR) protein database with a variety of query sequences, we have found many relationships that could not have been distinguished from chance by pairwise database search methods.

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“…as in Fig. 7 of the aspartic proteinases [38]. These enzymes contain an internal duplication so that the NH2-and COOH-lobes are topologically equivalent [39] and each contains the Asp-ThrGly sequence similar to the viral sequences.…”

Section: Endothiapepsin (C) Lpsftfgvgsarivipgdyidfgpistgssscfggiqssagmentioning

confidence: 99%

Knowledge‐based protein modelling and design

Blundell¹,

Carney²,

Gardner³

et al. 1988

European Journal of Biochemistry

244

116

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A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge-based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three-dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the 'average structure' or 'framework', builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem of ah initio design is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greekkey motifs.The characterisation, production and engineering of new proteins by recombinant DNA technology has revolutionised approaches to the design of novel molecules of industrial, agricultural and clinical interest. However, systematic design requires a blueprint or plan which must describe the molecular architecture. For this reason protein crystallography and modelling have become central to rational approaches to : (a) modelling of protein receptors for drugs, herbicides and insecticides; (b) design of protein and peptide vaccines; (c) protein engineering of novel molecules.Unfortunately a detailed experimental definition of the three-dimensional structure of a protein is time-consuming and expensive, and its success is usually dependent on the production of well ordered crystals suitable for X-ray diffraction although proteins may be studied by two-dimensional NMR techniques. On the other hand, molecular modelling has been unsuccessful when approached using ab initio techniques of simulation and prediction, At Birkbeck we are developing a systematic approach to molecular modelling and design that is dependent on structural homology and analogy. It utilises a knowledge-based approach derived from structures defined by X-ray analysis. It seeks to develop a relational data base of protein three-dimensional structures and a set of rules that can be used to assemble amino acid sequences, secondary structures, loops, domains and tertiary structures of unknown proteins in an hierarchical manner [I, 21.The value of an homologous protein structure in modelling was first recognised by Browne et al. [3] in the construc- tion of a model of a-lactalbumin based on the threedimensional structure of lysozyme. Similar methods have been used to define structural features of a range of proteins including insulin-like growth factors, serine proteinases, renins and histocompatibility antigens (see [2] for review). However, these ...

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Close structural resemblance between putative polymerase of a Drosophila transposable genetic element 17.6 and pol gene product of Moloney murine leukaemia virus.

Cited by 158 publications

References 37 publications

Nucleotide sequence characterization of a Drosophila retrotransposon, 412

Nucleotide sequence characterization of a Drosophila retrotransposon, 412

Protein database searches for multiple alignments.

Knowledge‐based protein modelling and design

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