Intrinsic secondary structure propensities of the amino acids, using statistical ϕ–ψ matrices: Comparison with experimental scales

Muñoz, Víctor; Serrano, Luís

doi:10.1002/prot.340200403

Cited by 300 publications

(243 citation statements)

References 26 publications

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“…LSP was mapped between 16183bp and inside region of the tRNA pro [16,33,35 ]. These results of the in-vitro generated transcription products presented in this study are also in good agreement with the previous reports [13,17,20,30] of the in-vivo transcription initiation products from the HSP/LSP containing the mt D-loop region spanning at one end of tRNA leu and the other end of tRNA thr . All of these results discussed here indicate that the LES invitro reconstituted transcription complex was able to transcribe bidirectionally from both Hstrand-promoter (HSP) and light-strand-promoter (LSP) which lie within the D-loop segment.…”

Section: Discussionsupporting

confidence: 92%

“…. In the in-vitro reconstituted transcription system (isolated by the heparin-sepharose chromatography), the HSP/LSP region (where both major and minor promoters lie within close proximity) of the mitochondrial Dloop segment in both human and mouse were reported previously to initiate transcription products which ranged between >100bp to 700bp runoff transcripts [13][14][15][16][17]19,20,29,30], although the mitochondrial lysate transcribed >2050bp ->3000bp [16] in an in vitro assay system. The mitochondrial lysate produced comparatively larger transcripts (>4-5kb) from HSP/LSP fused with larger human mitochondrial DNA segment [16].…”

Section: Introductionmentioning

confidence: 99%

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3D model of RNA polymerase and bidirectional transcription

Bhattacharya

2007

Biochemical and Biophysical Research Communications

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In the in-vitro mitochondrial (mt) transcription initiation system with mt RNA polymerase fraction and mt lysate, the transcription initiation products were shown to be synthesized bi-directionally from the only H-strand-promoter (HSP)/L-strand-promoter region (LSP) of the mitochondrial Dloop genome segment. These transcription products ranged between >100bp and >800bp with the purified mitochondrial RNA polymerase fraction, but were larger (>2030bp-4000bp) in size with the mitochondrial lysate in both human and mouse [references 1-20]. In this brief report, an invitro reconstituted mitochondrial transcription system purified by affinity chromatography (heparinsepharose) from mouse hypotetraploid letter Ehrlich ascites tumor cell mitochondria was shown to initiate transcription bidirectionally from the mitochondrial D-loop region (HSP/LSP), as evidenced by in-vitro generated transcription products. The in-vitro generated transcription products were separated by sequencing gel. But this in-vitro reconstituted transcription system was not studied beyond the D-loop region. A 3D model of the enzyme RNA polymerase was docked with both ATP and CTP. KeywordsMitochondrial D-loop region; In-vitro transcription; mt RNA polymerase; gel-mobility shift assay; 3D model Both human and mouse mitochondrial (mt) in-vitro reconstituted transcription system and mt lysate were shown to transcribe bidirectionally from D-loop region containing H-strandpromoter/L-strand-promoter (HSP/LSP) of mitochondrial genome .These transcripts ranged between >100bp and >3000bp in both human and mouse [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The D-loop distal genes were also transcribed in this system [16]. The nuclear coded RNA polymerase, RNase P and RNase MRP as well as several transcription factors have now been proposed to function in a co-ordinate fashion for the synthesis of the polycistronic RNA and its processing into individual RNA molecules [1][2][3][4][5][6][7][8][9][10][11][12]. The ideal human transcription complex [13] was described to constitute RNA polymerase, transcription factor TFB1M (or TFB2M having weaker activity than TFB2M), LSP/HSP template (1-741bp) and mt general transcription factor TFAM. The mouse homologs (or orthologs) mTfb1m and mTfb2m were identified [13]. The transcription termination was reported to occur by 34kd mt-TERM/mtTERF DNA binding protein [14,15], although 24kd Tf1 transcription factor, 48kd TAS-A protein (which binds to termination associated sequence of mt D-loop region) as well as other putative binding proteins (TAS-B, -C, -D, -E, -F, -G; A/B and F/G which bind to partially overlapping sites) in the mt D-loop segment were reported [15,16]. Two-to-three putative mitochondrial transcription termination 1 Corresponding author: Pradip Bhattacharya, Room Nos. 121, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India. Fax: 91-11-26165886; Tel: 91-11-26704529, Email address: ronaldraegon@yahoo.com Publisher's Disclaimer: This is a PDF file o...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

3D model of RNA polymerase and bidirectional transcription

Bhattacharya

2007

Biochemical and Biophysical Research Communications

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“…The challenge in this work was to find, for each position, a limited set of amino acid choices that would interact favorably with the peptide template residues, and most importantly with the other residues yet to be designed. The first selection criteria should have rendered residues that should have good ␤-strand propensities, i.e., ␤-branched residues (30). The second should result in the selection of those residues having a larger number of favorable combinations with the other 19 residues at the remaining three positions.…”

Section: Discussionmentioning

confidence: 99%

Combinatorial approaches: A new tool to search for highly structured β-hairpin peptides

Pastor

Paz

Lacroix

et al. 2002

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

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Here we present a combinatorial approach to evolve a stable ␤-hairpin fold in a linear peptide. Starting with a de novo-designed linear peptide that shows a ␤-hairpin structure population of around 30%, we selected four positions to build up a combinatorial library of 20 4 sequences. Deconvolution of the library using circular dichroism reduced such a sequence complexity to 36 defined sequences. Circular dichroism and NMR of these peptides resulted in the identification of two linear 14-aa-long peptides that in plain buffered solutions showed a percentage of ␤-hairpin structure higher than 70%. Our results show how combinatorial approaches can be used to obtain highly structured peptide sequences that could be used as templates in which functionality can be introduced.

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“…Multivariate analysis of protein polymorphism MAPP uses quantitative scales measuring six physicochemical properties to evaluate missense variants: (1) hydropathy (Kyte and Doolittle 1982); (2) polarity (Stryer 1995); (3) charge (Stryer 1995); (4) side-chain volume (Zamyatin 1972); (5) free energy in ␣-helical conformation (Muñoz and Serrano 1994); and (6) free energy in ␤-sheet conformation (Muñoz and Serrano 1994). We denote these scales by s k for k = 1, .…”

Section: Methodsmentioning

confidence: 99%

Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity

Stone¹,

Sidow²

2005

Genome Res.

347

319

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We find that the degree of impairment of protein function by missense variants is predictable by comparative sequence analysis alone. The applicable range of impairment is not confined to binary predictions that distinguish normal from deleterious variants, but extends continuously from mild to severe effects. The accuracy of predictions is strongly dependent on sequence variation and is highest when diverse orthologs are available. High predictive accuracy is achieved by quantification of the physicochemical characteristics in each position of the protein, based on observed evolutionary variation. The strong relationship between physicochemical characteristics of a missense variant and impairment of protein function extends to human disease. By using four diverse proteins for which sufficient comparative sequence data are available, we show that grades of disease, or likelihood of developing cancer, correlate strongly with physicochemical constraint violation by causative amino acid variants.[Supplemental material is available online at www.genome.org. A Java executable of MAPP and documentation are freely available for download at http://mendel.stanford.edu/supplementarydata/stone_MAPP_2005.]Missense mutations that impair protein function may result in disease. For diseases caused by such deleterious mutations, a simple but plausible model presents itself: The type of disease is dependent on when and where the protein's function is required in the organism. Given the type of disease, its severity is likely determined by at least three parameters: (1) the degree to which the function of the protein is impaired by the missense mutation; (2) variants of other genes that modulate the effect of the major locus, also referred to as genetic background; and (3) the environment. We present here a predictive statistical framework for the first of these parameters, impairment of protein function by missense mutations.Our study was motivated by several observations relevant to protein structure, function, and evolution, and by previous studies that addressed the relationship between the nature of missense variants, impairment of protein function, and resulting disease ( In aggregate, these studies suggest that mutations in evolutionarily conserved sites tend to impair protein function and lead to disease. There is also weak evidence that protein impairment and disease severity are somewhat correlated with the physicochemical difference between the original amino acid and the missense variant. However, no transparent, quantitative relationship between evolutionary constraint, functional impairment, and disease severity has been described. We believe that there has been a methodological barrier to uncovering such a relationship.Our analysis rests on two complementary ideas: (1) that differences in standard physicochemical properties between the "wild-type" amino acid and the missense variant are the root cause of functional impairment; and (2) that evolutionary variation among orthologs in the affected position is a sample ...

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Intrinsic secondary structure propensities of the amino acids, using statistical ϕ–ψ matrices: Comparison with experimental scales

Cited by 300 publications

References 26 publications

3D model of RNA polymerase and bidirectional transcription

3D model of RNA polymerase and bidirectional transcription

Combinatorial approaches: A new tool to search for highly structured β-hairpin peptides

Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity

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