Arginine


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Standard codons for R : AGA AGG CGA CGC CGG CGT

Substitution preferences:
All protein types:
Favoured Lys ( 2) Gln ( 1)
Neutral Asn ( 0) Glu ( 0) His ( 0)
Disfavoured Ala (-1) Ser (-1) Thr (-1) Met (-1) Asp (-2) Gly (-2) Leu (-2) Tyr (-2)
Pro (-2) Val (-3) Trp (-3) Phe (-3) Cys (-3) Ile (-3)

Intracellular proteins:
Favoured Lys ( 1)
Neutral Asp ( 0) Glu ( 0) Asn ( 0) Gly ( 0) His ( 0) Met ( 0) Pro ( 0) Gln ( 0)
Ala ( 0) Ser ( 0) Thr ( 0)
Disfavoured Cys (-1) Ile (-1) Val (-1) Trp (-1) Tyr (-1) Leu (-1) Phe (-2)

Extracellular proteins:
Favoured Lys ( 1)
Neutral Asn ( 0) Asp ( 0) Glu ( 0) Met ( 0) Gly ( 0) His ( 0) Ile ( 0) Ala ( 0)
Gln ( 0) Pro ( 0) Ser ( 0) Thr ( 0) Val ( 0) Tyr ( 0)
Disfavoured Phe (-1) Trp (-1) Leu (-1) Cys (-5)

Membrane proteins:
Favoured Lys ( 9) Gln ( 6) Trp ( 5) His ( 5) Asn ( 2) Glu ( 2) Asp ( 1)
Neutral Gly ( 0) Met ( 0)
Disfavoured Tyr (-1) Ala (-1) Ser (-1) Thr (-1) Cys (-1) Val (-2) Pro (-3) Ile (-3)
Leu (-3) Phe (-4)


Substitutions: Arginine is a positively charged, polar amino acid. It thus most prefers to substitute for the other positively charged amino acid Lysine, though in some circumstances it will also tolerate a change to other polar amino acids.

Note that a change from Arginine to Lysine is not always neutral. In certain structural or functional contexts, such a mutation can be devestating to protein stability of function (see below).

Role in structure: Arginine frequently plays an important role in structure. First, it can be considered to be somewhat amphipathic as the part of the side chain nearest to the backbone is long, carbon containing and hydrophobic, whereas the end of the side chain is positively charged. For this reason, one can find Arginines where part of the side-chain is buried, and only the charged portion is on the outside of the protein. However, this is by no means always the case, and generally Arginines prefer to be on the outside of proteins.

Arginines are also frequently involved in salt-bridges, where they pair with a negatively charged amino acid (such as Aspartate, shown below) to create stabilising hydrogen bonds, that can be important for protein stability.

Role in function: Arginines are quite frequent in protein active or binding sites. The positive charge means that they can interact with negatively charged non-protein atoms (e.g. anions or carboxylate groups).

It contains a complex guanidinium group on its side-chain that has a geometry and charge distribution that is ideal for binding negatively charged groups on phosphates (it is able to form multiple hydrogen bonds) A good example can be found in the src homology 2 (SH2) domains:

The two Arginines shown in the figure (155 and 175) make multiple hydrogen bonds with the phosphate (yellow and red moeity).

Note that in this context Arginine is not easily replaced by Lysine. Although Lysine can interact with phosphates, it contains only a single amino group, meaning it is more limited in the number of hydrogen bonds it can form. A change from Arginine to Lysine in some contexts can thus be disasterous.


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Please cite: M.J. Betts, R.B. Russell. Amino acid properties and consequences of subsitutions.
In Bioinformatics for Geneticists, M.R. Barnes, I.C. Gray eds, Wiley, 2003.
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