COMPUTATIONAL MOLECULARBIOLOGY

Conserved protein sequence motifs

SUBMITTED BY,
MITHILAA S
1ST MSc BIOCHEMISTRY
 CONSERVED SEQUENCES

• In evolutionary biology, conserved sequences are identical or similar sequences

 in nucleic acids (DNA and RNA) or proteins across species (
orthologous sequences), or within a genome (paralogous sequences), or
between donor and receptor taxa (xenologous sequences).

• Conservation indicates that a sequence has been maintained by 

natural selection.
• A highly conserved sequence is one that has remained relatively
unchanged far back up the phylogenetic tree, and hence far back in 
geological time.
• Examples of highly conserved sequences include the RNA components
 of ribosomes present in all domains of life, the homeobox sequences
widespread amongst Eukaryotes, and the tmRNA in Bacteria.
• The study of sequence conservation overlaps with the fields of genomics
, proteomics, evolutionary biology, phylogenetics, bioinformatics and 
mathematics.
A multiple sequence alignment of five mammalian histone H1 proteins
Sequences are the amino acids for residues 120-180 of the proteins. Residues that are
conserved across all sequences are highlighted in grey. Below each site (i.e., position) of the
protein sequence alignment is a key denoting conserved sites (*), sites with 
conservative replacements (:), sites with semi-conservative replacements (.), and sites with 
non-conservative replacements ( ).
 PROTEIN SEQUENCE MOTIFS
• In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is
widespread and usually assumed to be related to biological function of the
macromolecule. For example, an N-glycosylation site motif can be defined as Asn,
followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro
residue.
• Protein sequence motifs are signatures of protein families and can often be used as tools
for the prediction of protein function.

• The generalization and modification of already known motifs are becoming major
trends in the literature, even though new motifs are still being discovered at an
approximately linear rate.
• The emphasis of motif analysis appears to be shifting from metabolic enzymes, in which
motifs are associated with catalytic functions and thus often readily recognizable, to
structural and regulatory proteins, which contain more divergent motifs.
• The consideration of structural information increasingly
contributes to the identification of motifs and their sensitivity.
Genome sequencing provides the basis for a systematic analysis of
all motifs that are present in a particular organism.
• A systematically derived motif database is therefore feasible,
allowing the classification of the majority of the newly appearing
protein sequences into known families.
• Protein sequence motifs are signatures of protein families and can often be
used as tools for the prediction of protein function.

• The generalization and modification of already known motifs are

becoming major trends in the literature, even though new motifs are still
being discovered at an approximately linear rate.
• The emphasis of motif analysis appears to be shifting from metabolic
enzymes, in which motifs are associated with catalytic functions and thus
often readily recognizable, to structural and regulatory proteins, which
contain more divergent motifs.
• The consideration of structural information increasingly contributes to the
identification of motifs and their sensitivity.
Article
Conserved sequence motifs in the initiator proteins for rolling circle DNA
replication encoded by diverse replicons from eubacteria, eucaryotes and
archaebacteria

Abstract
An amino acid motif was identified that consists of the sequence
HisHydrHisHydrHydrHydr (Hydr--bulky hydrophobic residue) and is
conserved in two vast classes of proteins, one of which is involved in
initiation and termination of rolling circle DNA replication, or RCR
(Rep proteins), and the other in mobilization (conjugal transfer) of
plasmid DNA (Mob proteins). Based on analogies with
metalloenzymes, it is hypothesized that the two conserved His
residues in this motif may be involved in metal ion coordination
required for the activity of the Rep and Mob proteins. Rep proteins
contained two additional conserved motifs, one of which was located
upstream, and the other downstream from the 'two His' motif. The C-
terminal motif encompassed the Tyr residue(s) forming the covalent
link with nicked DNA.
REFERENCES
• Clustal FAQ #Symbols". Clustal. Archived from the original on
24 October 2016. Retrieved 8 December 2014.
•  Sanger, F. (24 September 1949). 
”Species Differences in Insulins”. Nature. 
•  Marmur, J; Falkow, S; Mandel, M (October 1963). “New
Approaches to Bacterial Taxonomy”. Annual Review of
Microbiology. 
•   Pace, N. R.; Sapp, J.; Goldenfeld, N. (17 January 2012). 
"Phylogeny and beyond: Scientific, historical, and conceptual
significance of the first tree of life"
. Proceedings of the National Academy of Sciences.
THANK YOU