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Proteome analysis of Mtb Extensive gene duplication, functional redundancy and diversification Precise function 40%, some functional info 44%, 16% unknown, probably Mycobacterial specific 9% genome encodes PE and PPE proteins (gly rich) Many fatty acid metabolism proteins >250 cf 50 in E.coli (reflection of cell wall) Has two hemoglobins for oxygen storage Mycobactins for iron Glyoxylate shunt NB for latency or persistence (isocitrate lyase)
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MYCOBACTERIUM TUBERCULOSIS PROTEOME
• M. tuberculosis- intracellular pathogen • - TB prevalent in Africa and Asia• - 1/3 population is infected • - 8 million new cases per year• Complete sequence is available in SPTR:• NCBI_TaxID=1773 (Rv=83332) (CDC1551=83331)• 4087 proteins in SPTR, 2706 are “hypothetical”• 66% of proteins in SPTR uncharacterised
Classification of hypothetical proteins
Q10401 PEPTIDASE B (EC 3.-.-.-). IPR000819 Cytosol aminopeptidaseO33261 L-ASPARAGINE PERMEASE. IPR002027 Amino acid permeaseQ11018 HYPOTHETICAL ABC TRANSPORTER. IPR001617 ABC transporters familyP96936 HYPOTHETICAL 54.8 KD PROTEIN. IPR002106 Aminoacyl-transfer RNA synthetases class-IIP96255 ACETATE KINASE (EC 2.7.2.1). IPR000890 Acetate and butyrate kinaseQ10535 HYPOTHETICAL PROTEIN RV0873. IPR001552 Acyl-CoA dehydrogenaseQ10974 PROBABLE THIOESTERASE RV2928 (EC 3.1.2.-). IPR001031 ThioesteraseQ50705 ALANINE RACEMASE (EC 5.1.1.1). IPR000821 Alanine racemaseQ11024 HYPOTHETICAL 67.7 KD PROTEIN. IPR001633 Domain of unknown function P71571 HYPOTHETICAL 83.6 KD PROTEIN. IPR000977 ATP-dependent DNA ligaseQ50720 HYPOTHETICAL 20.6 KD PROTEIN RV3405C. IPR001647 Bacterial regulatory proteins, TetRM. tuberculosis proteome = 3784 proteins
- 2505 have InterPro matches (64.7%)- Of those in InterPro, at least 860 hypothetical can be characterised- 33% of hypothetical proteins in SPTR, or 22% proteome
Proteome analysis of Mtb
• Extensive gene duplication, functional redundancy and diversification
• Precise function 40%, some functional info 44%, 16% unknown, probably Mycobacterial specific
• 9% genome encodes PE and PPE proteins (gly rich)• Many fatty acid metabolism proteins >250 cf 50 in E.coli
(reflection of cell wall)• Has two hemoglobins for oxygen storage• Mycobactins for iron• Glyoxylate shunt NB for latency or persistence (isocitrate
lyase)
Structural information
• 1079 ORFs can be assigned to SCOP -1566 domains, 1639 regions
• 482 (12.4%) have hits in HSSP• 9 (0.2%) have hits in PDB
Venn diagram of InterPro hits for the 3 organisms
E.coli
M.tuberB. sub
675
68125
62
129
76
59
Protein secretion systemFlagellar proteinsGram -ve porinsLypolytic enzymesSpecific transposases
PE/PPE proteinsDisease resistance proteinCytochrome B5Specific transposases
Tet resistance proteinSpore proteinsStaph nucleasePectate lyase
Differences:
-Glycosol hydrolases-Proteases-Transcription factors-Transporters-Oxygenases
Pie charts of whole proteome analysis of 4 organisms
Distribution of protein functions
Met
abol
ism
Reg
ulat
ion
DN
A/R
NA
met
abol
ism
Cel
l cyc
le
Def
ense
/Pat
hoge
nesi
s
Stru
ctur
al
Mis
cella
neou
s
Pro
tein
fold
ing/
degr
adat
ion
Sig
nal t
rans
duct
ion
Tran
spor
t
Unk
now
n
M. tuberculosisE. coli
B. subtilisS. cerevisae0
5
10
15
20
25
M. tuberculosis
E. coli
B. subtilis
S. cerevisae