Introduction Role of domains in PROTEIN EVOLUTION Reuse of particular domain Subunit sharing New domain combinations Regulation of protein expression by domain shuffling Syntactical and semantic shift in the function of proteins

1. MODULAR NATURE OF
PROTEINS By
S.M.SHEIKHASINAH

2. ?????.....

3. CONTENTS!
 Introduction
 Role of domains in PROTEIN EVOLUTION
 Reuse of particular domain
 Subunit sharing
 New domain combinations
 Regulation of protein expression by domain
shuffling
 Syntactical and semantic shift in the function
of proteins

4. 1.
Introduction

5. “Function of a protein ???
Domains and nature of their interactions

6. Domain
 Proteins are composed of evolutionary units called domains
 Can either have an independent function or contribute to the
function of a multidomain protein in cooperation with other
domains.
 Once a domain has duplicated, it can evolve a new or
modified function.
 Based on sequence, structural and functional evidence are
grouped into superfamilies.

7. ROLE OF
DOMAINS Acquiring new sructures and function by combination of
domain

8. ☺ Formation of new domain combinations is an important mechanism
in protein evolution.
☺ Proteins contain several thousand different combinations of two
superfamilies.
☺ Duplication is one of the main sources for creation of new proteins.
☺ After duplication ,it evolve a new or modified function either by
sequence divergence or by combining with other domains to form a
multidomain protein with a new series of domains.
☺ Formation of multidomain proteins by duplication and recombination,
and the geometry and functional relationships .
☺ Supradomains are two- or three-domain combinations that occur in
different domain architectures with different N- and C-terminal
neighbours.
New domain
combinatons

9. Overview of different aspects of
multidomain proteins :
Domains belonging to the same
superfamily are represented as
rectangles of the same colour. {1}
Supradomains are two- or three-
domain combinations that occur in
different domain architectures {2}
Forms different geometry with
different functions.{3}
These domains forms a functional
units{4}

10. Reuse of particular
domains

11. A few domain
superfamilies are highly
versatile and have
neighbouring domains
from many
superfamilies.
Each superfamily has
its own feature.
* Some superfamilies
are highly versatile,
some are highly
abundant and some
superfamilies are both.
* It depends on the
structure and function
of the domains and
domain combinations
that determine the
selection.

12. Cntd…
• Important examples of the reuse of particular domains
come from signal transduction.
&.The SH3 and SH2 domains in signal transduction.
&. Combination and addition of several domains
determine the versatility of the protein.

13. To have the SAME
FUNCTION
-- Sequential order of
domains are conserved

14.  If the same domain combination is
observed in two different
proteins,they are closely related with
each other phylogenetically.
* Domain architecture have evolved
from the same ancestor.
* EG:Rossmann fold
* Proteins sharing the same series
of domains tend to have the same
function.

15. Geometry of domain
combinations

16. ~Sequential order of domains are largely conserved.
~The geometry of Rossmann domains and their
partner domains -conserved - same superfamily.
~~Proteins of unknown structure - based on
homologous polypeptide(s) of known structure.
*EG :yeast ribosome and exosome
~the more similar the domain sequences -interaction
of protein domains is more conserved.

17. Functional relationships of
domains in multi-domain
proteins!

18. @.Domain-centric scheme emphasises domain function.
In this domain-centric functional classification scheme, domains are
classified into several categories
1.catalytic activity,
2. cofactor binding,
3.responsibility for subcellular localisation,
4. protein–protein interaction etc..
TWO principle
1. A domain can perform the same function, but in different protein contexts
(i.e. with different partner domains).Eg:sensory, regulatory and enzymatic
domains.
2. Some domains modify their function according to the partner
domain.Eg:WHD domain (Winged Helix Domain)

19. Place your screenshot here
Syntactical and semantic
shift
1.WHD with Restriction endonuclease.-
FokI protein
2.WHD with sensory or regulatory
domain-FadR
3. Performs the same role (i.e. it
targets the protein to a specific
sequence), but the range of
functions is achieved by combining
the WHD with different partner
domains, so it is exhibiting a
syntactical shift.
4. ) A semantic shift is found in
human methionine aminopeptidase -
WHD acts as a substrate specificity
pocket -no DNA-binding activity

20. THANK YOU