Posttranslational modification Protein primary structure

fig. 1 n-terminal acetylation



acetylation




−
c
(
=
o
)
−
c

h

3





{\displaystyle \mathrm {-c(=o)-ch_{3}} }




the positive charge on n-terminal amino group may eliminated changing acetyl group (n-terminal blocking).


formylation




−
c
(
=
o
)
h



{\displaystyle \mathrm {-c(=o)h} }




the n-terminal methionine found after translation has n-terminus blocked formyl group. formyl group (and methionine residue itself, if followed gly or ser) removed enzyme deformylase.


pyroglutamate


fig. 2 formation of pyroglutamate n-terminal glutamine



an n-terminal glutamine can attack itself, forming cyclic pyroglutamate group.


myristoylation




−
c
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=
o
)
−


(
c

h

2


)


12


−
c

h

3





{\displaystyle \mathrm {-c(=o)-\left(ch_{2}\right)_{12}-ch_{3}} }




similar acetylation. instead of simple methyl group, myristoyl group has tail of 14 hydrophobic carbons, make ideal anchoring proteins cellular membranes.

the c-terminal carboxylate group of polypeptide can modified, e.g.,

fig. 3 c-terminal amidation



amidation (see figure)


the c-terminus can blocked (thus, neutralizing negative charge) amidation.


glycosyl phosphatidylinositol (gpi) attachment


glycosyl phosphatidylinositol large, hydrophobic phospholipid prosthetic group achors proteins cellular membranes. attached polypeptide c-terminus through amide linkage connects ethanolamine, thence sundry sugars , phosphatidylinositol lipid moiety.

finally, peptide side chains can modified covalently, e.g.,

phosphorylation


aside cleavage, phosphorylation perhaps important chemical modification of proteins. phosphate group can attached sidechain hydroxyl group of serine, threonine , tyrosine residues, adding negative charge @ site , producing unnatural amino acid. such reactions catalyzed kinases , reverse reaction catalyzed phosphatases. phosphorylated tyrosines used handles proteins can bind 1 another, whereas phosphorylation of ser/thr induces conformational changes, presumably because of introduced negative charge. effects of phosphorylating ser/thr can simulated mutating ser/thr residue glutamate.


glycosylation


a catch-all name set of common , heterogeneous chemical modifications. sugar moieties can attached sidechain hydroxyl groups of ser/thr or sidechain amide groups of asn. such attachments can serve many functions, ranging increasing solubility complex recognition. glycosylation can blocked inhibitors, such tunicamycin.


deamidation (succinimide formation)


in modification, asparagine or aspartate side chain attacks following peptide bond, forming symmetrical succinimide intermediate. hydrolysis of intermediate produces either asparate or β-amino acid, iso(asp). asparagine, either product results in loss of amide group, hence deamidation .


hydroxylation


proline residues may hydroxylates @ either of 2 atoms, can lysine (at 1 atom). hydroxyproline critical component of collagen, becomes unstable upon loss. hydroxylation reaction catalyzed enzyme requires ascorbic acid (vitamin c), deficiencies in lead many connective-tissue diseases such scurvy.


methylation


several protein residues can methylated, notably positive groups of lysine , arginine. methylation @ these sites used regulate binding of proteins nucleic acids. lysine residues can singly, doubly , triply methylated. methylation not alter positive charge on side chain, however.


acetylation


acetylation of lysine amino groups chemically analogous acetylation of n-terminus. functionally, however, acetylation of lysine residues used regulate binding of proteins nucleic acids. cancellation of positive charge on lysine weakens electrostatic attraction (negatively charged) nucleic acids.


sulfation


tyrosines may become sulfated on





o

η





{\displaystyle \mathrm {o^{\eta }} }

atom. unusually, modification occurs in golgi apparatus, not in endoplasmic reticulum. similar phosphorylated tyrosines, sulfated tyrosines used specific recognition, e.g., in chemokine receptors on cell surface. phosphorylation, sulfation adds negative charge neutral site.


prenylation , palmitoylation




−
c
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=
o
)
−


(
c

h

2


)


14


−
c

h

3





{\displaystyle \mathrm {-c(=o)-\left(ch_{2}\right)_{14}-ch_{3}} }




the hydrophobic isoprene (e.g., farnesyl, geranyl, , geranylgeranyl groups) , palmitoyl groups may added





s

γ





{\displaystyle \mathrm {s^{\gamma }} }

atom of cysteine residues anchor proteins cellular membranes. unlike gpi , myritoyl anchors, these groups not added @ termini.


carboxylation


a relatively rare modification adds carboxylate group (and, hence, double negative charge) glutamate side chain, producing gla residue. used strengthen binding hard metal ions such calcium.


adp-ribosylation


the large adp-ribosyl group can transferred several types of side chains within proteins, heterogeneous effects. modification target powerful toxins of disparate bacteria, e.g., vibrio cholerae, corynebacterium diphtheriae , bordetella pertussis.


ubiquitination , sumoylation


various full-length, folded proteins can attached @ c-termini sidechain ammonium groups of lysines of other proteins. ubiquitin common of these, , signals ubiquitin-tagged protein should degraded.

most of polypeptide modifications listed above occur post-translationally, i.e., after protein has been synthesized on ribosome, typically occurring in endoplasmic reticulum, subcellular organelle of eukaryotic cell.

many other chemical reactions (e.g., cyanylation) have been applied proteins chemists, although not found in biological systems.