Beruflich Dokumente
Kultur Dokumente
Department of Bio-Informatics
Topic Post-Translational
Modifications
POST-TRANSLATIONAL MODIFICATIONS
INTRODUCTION:
Primary structure of a protein obtained from human genome project is not
sufficient to explain its various biological functions or their regulation mechanisms.
Cellular homeostatic modifications of proteins have been shown to initiate various
cellular processes. Post-translational modifications (PTMs) of proteins, call the covalent
modifications of amino acids collectively. Protein was thought to have a linear polymer
decorated with simple modification; however, very complicated modifications in one
protein are lately discovered in many processes. A variety of chemical modifications have
been observed in a protein and these modifications alone or in various combinations occur
in a time-and signal-dependent manner. PTMs of proteins determine their tertiary and
quaternary structures and regulate their activities and functions.
Synthesis will continue and if the protein is secreted it will end up completely in the
lumen of the ER. If the protein is membrane associated a stop transfer motif in the protein
will stop the transfer of the protein through the ER membrane. This will become the
membrane spanning domain of the protein.”
1. Proteolytic Cleavage:
2. Glycoprotein:
found within a consensus sequence of amino acids, N-X-S (T), where X is any amino acid
except proline. N-linked glycoproteins all contain a common core of carbohydrate
attached to the polypeptide. This core consists of three mannose residues and two
GlcNAc. A variety of other sugars is attached to this core and comprises three major N-
linked families:
• High-mannose type: contains all mannose outside the core in varying amounts.
• Hybrid type: contains various sugars and amino sugars.
• Complex type: is similar to the hybrid type, but in addition, contains sialic acids to
varying degrees.
Most proteins that are secreted or bound to the plasma membrane are modified by
carbohydrate attachment. The part that modified, in plasma membrane-bound proteins, is
the extra cellular portion of plasma membrane bound proteins that is modified.
Intracellular proteins are less frequently modified by carbohydrate attachment. However,
the attachment of carbohydrate to intracellular proteins confers unique functional
activities on these proteins. Linkage of carbohydrate to cytosolic and/or nuclear proteins
occurs via O-linkage and involves attachment of GlcNAc to serine or threonine residues.
The linkage is catalyzed by the enzyme O-GlcNAc transferase OGT. Several transcription
factors and RNA polymerase II have been shown to be modified by O-GlcNAc linkage.
Enzymes that are destined for the lysosomes or Lysosomal enzymes are directed
there by a specific carbohydrate modification.
Two distinct Man-6-P receptors have been identified. Both are integral membrane
proteins. One receptor is large with a molecular weight of approximately 275,000
Daltons. The other receptor is smaller with a molecular weight of approximately 46,000
Daltons. Evidence indicates that both receptors function to target newly synthesized
Lysosomal enzymes to the lysosomes.
4. Acylation:
Many proteins are modified at their N-termini following synthesis. In most cases
the initiator methionine is hydrolyzed and an acetyl group is added to the new N-terminal
amino acid. Acetyl-CoA is the acetyl donor for these reactions. Some proteins have the 14
carbon myristoyl group added to their N-termini. The donor for this modification is
myristoyl-CoA. This latter modification allows association of the modified protein with
membranes. The catalytic subunit of cyclic AMP-dependent protein kinase (PKA) is
myristoylated.
5. Methylation:
6. Phosphorylation:
In animal cells serine, threonine and tyrosine are the amino acids subject to
Phosphorylation.
7. Sulfation:
8. Prenylation:
Prenylation refers to the addition of the 15 carbon farnesyl group or the 20 carbon
geranylgeranyl group to acceptor proteins, both of which are isoprenoid compounds
derived from the cholesterol biosynthetic pathway. The isoprenoid groups are attached to
cysteine residues at the carboxy terminus of proteins in a thioether linkage (C-S-C). A
common consensus sequence at the C-terminus of prenylated proteins has been identified
and is composed of CAAX, where C is cysteine, A is any aliphatic amino acid, except
alanine, and X is the C-terminal amino acid. In order for the Prenylation reaction to occur
the three C-terminal amino acids (AAX) are first removed and the cysteine is activated by
methylation in a reaction utilizing S-adenosylmethionine as the methyl donor.
11. Selenoproteins:
REFERNCES:
http://www.med.unibs.it/~marchesi/protmod.html
http://www.modares.ac.ir/elearning/mnaderi/Genetic Engineering
courseII/Pages/post-translational_modification.htm
Wikipedia.org