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PMID: 10931922 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Proteomics of Mycoplasma genitalium: identification and characterization of unannotated and atypical proteins in a small model genome.

Nucleic acids research ·Vol. 28 ·No. 16 ·2000-08-15 ·Pages 3075-82

Balasubramanian S, Schneider T, Gerstein M, Regan L

Abstract

We present the results of a comprehensive analysis of the proteome of Mycoplasma genitalium (MG), the smallest autonomously replicating organism that has been completely sequenced. Our aim was to identify and characterize all soluble proteins in MG that are structurally and functionally uncharacterized. We were particularly interested in identifying proteins that differed significantly from typical globular proteins, for example, proteins which are unstructured in the absence of a 'partner' molecule or those that exhibit unusual thermodynamic properties. This work is complementary to other structural genomics projects whose primary aim is to determine the three-dimensional structures of proteins with unknown folds. We have identified all the full-length open reading frames (ORFs) in MG that have no homologs of known structure and are of unknown function. Twenty-five of the total 483 ORFs fall into this category and we have expressed, purified and characterized 11 of them. We have used circular dichroism (CD) to rapidly investigate their biophysical properties. Our studies reveal that these proteins have a wide range of structures varying from highly helical to partially structured to unfolded or random coil. They also display a variety of thermodynamic properties ranging from cooperative unfolding to no detectable unfolding upon thermal denaturation. Several of these proteins are highly conserved from mycoplasma to man. Further information about target selection and CD results is available at http://bioinfo.mbb.yale.edu/genome

MeSH Terms
Amino Acid Sequence Animals Bacterial Proteins/chemistry,genetics Conserved Sequence Genome, Bacterial Humans Molecular Sequence Data Mycoplasma/genetics Open Reading Frames Proteome/genetics Sequence Alignment Sequence Homology, Amino Acid Thermodynamics
Chemicals
Bacterial Proteins Proteome
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Balasubramanian S
Department of Molecular Biophysics and Biochemistry, Department of Computer Science and Department of Chemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520-8114, USA.
Schneider T
Gerstein M
Regan L
References (54)
54 references, click to expand
  1. Structural genomics and its importance for gene function analysis.
    Nat Biotechnol. 2000 Mar;18(3):283-7 PMID: 10700142
  2. DIVCLUS: an automatic method in the GEANFAMMER package that finds homologous domains in single- and multi-domain proteins.
    Bioinformatics. 1998;14(2):144-50 PMID: 9545446
  3. Role of the structural domain of troponin C in muscle regulation: NMR studies of Ca2+ binding and subsequent interactions with regions 1-40 and 96-115 of troponin I.
    Biochemistry. 2000 Mar 21;39(11):2902-11 PMID: 10715110
  4. Structural proteomics: prospects for high throughput sample preparation.
    Prog Biophys Mol Biol. 2000;73(5):339-45 PMID: 11063779
  5. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins.
    Annu Rev Biophys Biophys Chem. 1986;15:321-53 PMID: 3521657
  6. Improved tools for biological sequence comparison.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 PMID: 3162770
  7. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  8. Predicting coiled coils from protein sequences.
    Science. 1991 May 24;252(5009):1162-4 PMID: 2031185
  9. Structural genomics: beyond the human genome project.
    Nat Genet. 1999 Oct;23(2):151-7 PMID: 10508510
  10. Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.
    J Mol Biol. 1999 Oct 22;293(2):321-31 PMID: 10550212
  11. Global transposon mutagenesis and a minimal Mycoplasma genome.
    Science. 1999 Dec 10;286(5447):2165-9 PMID: 10591650
  12. Rational structural genomics: affirmative action for ORFans and the growth in our structural knowledge.
    Protein Eng. 1999 Dec;12(12):1029-30 PMID: 10611394
  13. From genes to protein structure and function: novel applications of computational approaches in the genomic era.
    Trends Biotechnol. 2000 Jan;18(1):34-9 PMID: 10631780
  14. Biological function made crystal clear - annotation of hypothetical proteins via structural genomics.
    Curr Opin Biotechnol. 2000 Feb;11(1):25-30 PMID: 10679350
  15. Homology-based fold predictions for Mycoplasma genitalium proteins.
    J Mol Biol. 1998 Jul 17;280(3):323-6 PMID: 9665839
  16. Removing near-neighbour redundancy from large protein sequence collections.
    Bioinformatics. 1998 Jun;14(5):423-9 PMID: 9682055
  17. Thousands of proteins likely to have long disordered regions.
    Pac Symp Biocomput. 1998;:437-48 PMID: 9697202
  18. Protein disorder and the evolution of molecular recognition: theory, predictions and observations.
    Pac Symp Biocomput. 1998;:473-84 PMID: 9697205
  19. Shining a light on structural genomics.
    Nat Struct Biol. 1998 Aug;5 Suppl:643-5 PMID: 9699614
  20. Mycoplasma gene expression in Escherichia coli.
    Methods Mol Biol. 1998;104:259-65 PMID: 9711662
  21. Class-directed structure determination: foundation for a protein structure initiative.
    Protein Sci. 1998 Sep;7(9):1851-6 PMID: 9761466
  22. Multiple sequence alignment with Clustal X.
    Trends Biochem Sci. 1998 Oct;23(10):403-5 PMID: 9810230
  23. Advances in refolding of proteins produced in E. coli.
    Curr Opin Biotechnol. 1998 Oct;9(5):497-501 PMID: 9821278
  24. Proteins. One thousand families for the molecular biologist.
    Nature. 1992 Jun 18;357(6379):543-4 PMID: 1608464
  25. Non-globular domains in protein sequences: automated segmentation using complexity measures.
    Comput Chem. 1994 Sep;18(3):269-85 PMID: 7952898
  26. SCOP: a structural classification of proteins database for the investigation of sequences and structures.
    J Mol Biol. 1995 Apr 7;247(4):536-40 PMID: 7723011
  27. The minimal gene complement of Mycoplasma genitalium.
    Science. 1995 Oct 20;270(5235):397-403 PMID: 7569993
  28. Analysis of compositionally biased regions in sequence databases.
    Methods Enzymol. 1996;266:554-71 PMID: 8743706
  29. A minimal gene set for cellular life derived by comparison of complete bacterial genomes.
    Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10268-73 PMID: 8816789
  30. MultiCoil: a program for predicting two- and three-stranded coiled coils.
    Protein Sci. 1997 Jun;6(6):1179-89 PMID: 9194178
  31. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases.
    Nature. 1997 Jun 19;387(6635):814-9 PMID: 9194563
  32. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  33. The complete genome sequence of Escherichia coli K-12.
    Science. 1997 Sep 5;277(5331):1453-62 PMID: 9278503
  34. 100,000 protein structures for the biologist.
    Nat Struct Biol. 1998 Dec;5(12):1029-32 PMID: 9846869
  35. Structural assignments to the Mycoplasma genitalium proteins show extensive gene duplications and domain rearrangements.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14658-63 PMID: 9843945
  36. The CATH Database provides insights into protein structure/function relationships.
    Nucleic Acids Res. 1999 Jan 1;27(1):275-9 PMID: 9847200
  37. Patterns of protein-fold usage in eight microbial genomes: a comprehensive structural census.
    Proteins. 1998 Dec 1;33(4):518-34 PMID: 9849936
  38. Structure-based assignment of the biochemical function of a hypothetical protein: a test case of structural genomics.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15189-93 PMID: 9860944
  39. Estimating the number of protein folds.
    J Mol Biol. 1998 Dec 18;284(5):1301-5 PMID: 9878351
  40. Structural genomics: keystone for a Human Proteome Project.
    Nat Struct Biol. 1999 Jan;6(1):11-2 PMID: 9886282
  41. How representative are the known structures of the proteins in a complete genome? A comprehensive structural census.
    Fold Des. 1998;3(6):497-512 PMID: 9889159
  42. Distribution of protein folds in the three superkingdoms of life.
    Genome Res. 1999 Jan;9(1):17-26 PMID: 9927481
  43. GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences.
    J Mol Biol. 1999 Apr 9;287(4):797-815 PMID: 10191147
  44. Comparing genomes in terms of protein structure: surveys of a finite parts list.
    FEMS Microbiol Rev. 1998 Oct;22(4):277-304 PMID: 10357579
  45. Advances in structural genomics.
    Curr Opin Struct Biol. 1999 Jun;9(3):390-9 PMID: 10361097
  46. Estimating the total number of protein folds.
    Proteins. 1999 Jun 1;35(4):408-14 PMID: 10382668
  47. A phylogenetic approach to target selection for structural genomics: solution structure of YciH.
    Nucleic Acids Res. 1999 Oct 15;27(20):4018-27 PMID: 10497266
  48. CATH--a hierarchic classification of protein domain structures.
    Structure. 1997 Aug 15;5(8):1093-108 PMID: 9309224
  49. Assigning folds to the proteins encoded by the genome of Mycoplasma genitalium.
    Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11929-34 PMID: 9342339
  50. The complete genome sequence of the gram-positive bacterium Bacillus subtilis.
    Nature. 1997 Nov 20;390(6657):249-56 PMID: 9384377
  51. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
    Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 PMID: 9396791
  52. Marrying structure and genomics.
    Structure. 1998 Mar 15;6(3):259-63 PMID: 9551548
  53. The Argonne Structural Genomics Workshop: Lamaze class for the birth of a new science.
    Structure. 1998 Mar 15;6(3):265-7 PMID: 9551549
  54. Intrinsic structural disorder of the C-terminal activation domain from the bZIP transcription factor Fos.
    Biochemistry. 2000 Mar 14;39(10):2708-13 PMID: 10704222
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/28.16.3075
Published
2000-08-15
Pages
3075-82
Language
English
Region
England
NLM ID
0411011
PMCID
PMC108442
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/28.16.3075 PMC Full Text View journal details
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