common peptides study of aminoacyl-trna synthetases
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Common peptides study of aminoacyl-tRNA synthetases
Assaf Gottlieb, Milana Frenkel-Morgenstern,Mark Safro, David Horn, Plos One, 2011
* Figure from Prous science
Aminoacyl-tRNA synthetases (aaRSs)
Rosetta stone
aaRS classes• Divided into two classes (I & II),
characterized by different structures and distinguishing motifs
NameClass
Threonyl tRNA synthetaseII
Lysyl tRNA synthetase *II
Alanyl tRNA synthetaseII
Seryl tRNA synthetaseII
Aspartatyl tRNA synthetaseII
Glycyl tRNA synthetaseII
Prolyl tRNA synthetaseII
Phenylalanyl tRNA synthetaseII
Histidyl tRNA synthetaseII
Asparaginyl tRNA synthetaseII
NameClass
Tyrosyl tRNA synthetaseI
Tryptophanyl tRNA synthetaseI
Leucyl tRNA synthetaseI
Isoleucyl tRNA synthetaseI
Valyl tRNA synthetaseI
Methionyl tRNA synthetaseI
Cysteinyl tRNA synthetaseI
Glutamyl tRNA synthetaseI
Glutaminyl tRNA synthetaseI
Arginyl tRNA synthetaseI
• DataData
• Method
• Results
Data
• 5,406 non-redundant aaRS protein sequences
• ~500 species
• 22 aaRSs – 20 standard– Pyrrolysine– O-phosphoseryl-tRNA synthetase (SepRS))
• Data
• MethodMethod
• Results
MEX-Motif Extraction algorithm
a l i c e w a s b e g i n n i n g t o g e t v e r y t i r e d o f s i t t i n g b y h e r s i s t e r o n t h e b a n k a n d o f h a v i n g n o t h i n g t o d o o n c e o r t w i c e
s h e h a d p e e p e d i n t o t h e b o o k h e r
s i s t e r w a s r e a d i n g b u t i t h a d n o p i c t u r e s o r c o n v e r s a t i o n s i n i t a n d w h a t i s t h e u s e o f a b o o k t h o u g h t a l i c e w i t h o u
t p i c t u r e s o r c o n v e r s a t i o n
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Initially developed for learning text.
given a sequence of lettersgiven a sequence of letters
• = ∑ {a-z}
Creating the graph…
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structured graph
a
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{1003;3}
{1002;1}
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{1003;8}
{1003;7}
{1003;9}
{1003;10}
{1003;11}
{1003;12}
{1003;13}
{1003;14}
Creating the graph… - cont’d
MEX algorithm for proteins
Finds deterministic motifs (peptides)
Method of Common Peptides (CPs)
• Extract per-aaRS peptides to form 22 per-aaRS peptide lists
• Merge the 22 lists
• Search the merged list peptides on all aaRSs
• CP-space: 5,406 sequences x 10,612 CPs.
• Data
• Method
• ResultsResults
Inter-aaRSs similarity
Heat map of Pearson cross-correlations of different aaRSs according to their shared CPs.
* Self correlations were left out for cleaner view.
Class I
Class II
BLAST provides a complementary view
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aaRSs similarity-Eukaryotes
aaRSs similarity - Archaea
aaRSs similarity - Mitochondria
CPs & Mitochondrial aaRSs• Tested enrichment of mitochondrial CPs in
kingdom-specific CPs.
• 16 mitochondrial aaRSs enriched in Bacteria, 13 in α-proteobacteria
• 4 aaRSs enriched in Eukaryotes, none in Archaea
• Assessed which gene was retained for 5/8 aaRSs with single nuclear genes in higher eukaryotes.
Biotin-[acetyl-CoA carboxylase] synthetase (birA) and aaRSs
• Structural similarity between birA and class II aaRSs was reported, but no sequence homology.
• Extracted CPs from 1,630 birA sequences.
• 28 CPs are common (p<2e-5)
birA and aaRSs, contd.
CP(alternatives)
Structuralproperties
# of aaRSsoccurrences
# of birAoccurrences
# of class Ioccurrences
# of class IIoccurrences
GILIE (GILVEGILTE)
Biotin binding site in birA, ThrAMS binding site in ThrRS
21982113
GALRL(GALLL)
Binding site for 4AD in AspRS
132042
GEALG(GETLG)
Helix-turn-Helix in birA
422131
CPs as novel class signatures CP
# of class I aaRSs
# of class I occurrences
# of class II aaRSs
# of class II occurrences
TADEI**84711ALADE83712
KSLGN750022SKSKG729900SKGNV718200DVIAR**77300DVVAR**76012ADAIR73900
GLDLL73511GVERL*00892DLVEE*13766GLDRI*11743AEAVL12724ERISA*00724LRLAE**00638AAGVR22647
*Overlap a binding site** less than four residues apart from a binding site
Class I signatures Class II signatures
Functional role of CPs
• 29/50 prevalent CPs overlap known catalytic and binding sites (p<e-5)
• Additional 8 <4 residues from site (p<e-10)
• Most hit amino acid esterification sites• Other hit tRNA or ions binding sites.
Summary
• CP methodology identifies significant deterministic motifs.
• These motifs characterize family and class specific sequences.
• CPs can find subtle evolutionary traces
• CPs overlap functional sites
Thank you
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