Which amino acid would likely be found in the transmembrane portion of a protein?

The complete crystallised structure of LAT is still not published because it is still very difficult to crystallise membrane proteins. Therefore, we can only predict possible secondary structures and functions of LAT.

Inhaltsverzeichnis Show

• What amino acids are in transmembrane proteins?
• What type of amino acid would you expect to find in the transmembrane portion of a membrane protein?
• What does a transmembrane protein contain?
• What proteins are also called transmembrane proteins?

The protein structure homology-modeling servers that we used to analyse the amino acid sequence of LAT are “Swiss-Model”, JPRED3 and Kyte-Doolittle.

Figure. 1: Swiss-Model graph of linker for activation of T-cells family member 1 isoform a [Homo sapiens].H represents helix, C represents coiled and E represents extended β-strands.

In theory, the membrane-spanning region is frequently an α-helix comprising of around 20 amino acid residues. When data on 3-D structure is absent the presence of transmembrane α-helical segments in membrane protein can be predicted by looking for amino acid sequences in regions that are hydrophobic (high hydropathy values) [1].

Here, strong peaks are observed for this membrane protein. We anticipate that they are constructed from helices arisen from 23 amino acids (red). The finding is in agreement with the information obtained from JPRED3 and Kyte-Doolittle as shown below. Extended β-strands are also predicted to be located at 48-52, 132-135, 191-193 amino acids.

Figure 2: Predicted Hydrophathy plot of linker for activation of T-cells family member 1 isoform a [Homo sapiens]from Kyte-Doolittle.

A large positive hydropathic index is indicative of a hydrophobic region of the polypeptide chain, whereas a large negative value is indicative of a hydrophilic region [1]. The red square indicates a possible transmembrane α-helical region.

Figure 3: Predicted secondary structures of linker for activation of T-cells family member 1 isoform a [Homo sapiens] by JPRED3.

We can see a concrete agreement of the structure of the α-helices in LAT.

As the average length of an α-helix is 0.15 nm per amino acid residue, an α-helical sequence of 20 to 25 residues is long enough to span the thickness (3 nm) of the lipid bilayer [2]. A polypeptide chain surrounded by lipids, having no water molecules with which to hydrogen-bond, will tend to form α-helices or β-sheets, in which intrachain hydrogen bonding is maximized. If the side chains of all amino acids in a helix are nonpolar, hydrophobic interactions with the surrounding lipids further stabilise the helix.

Corresponding β-strands here that are also present in the Swiss-Model graph are the amino acids at 48-52, 132-135, 162-164, 171-173 and 191-193.

Interestingly, there appears to be 2 distinct phosphorylation motifs (YVNV) in LAT, which are involved with β-strands at the same time (171-173 and 191-193). They are likely to function as binding sites for recruiting other proteins that have domains that can recognise phosphotyrosine residues (i.e. SH2 domains)

Figure 4: Stereo, space-filling representation of an α-helical segment of LAT determined by X-ray crystal structure analysis. Backbone atoms are coloured according to type (N purple, O red, and H white) and the side chain atoms are gold [3].

Figure 5: Ribbon diagram of a helical signal-anchor for type III membrane protein [3].

The 3-D structure of the α-helices of LAT is provided by membranome database.

The prediction of the transmembrane segment is based on the fact that amino acids have preferred locations in transmembrane helices. Hydrophobic amino acids (Ala, Val, Leu, Ile, and Phe) often reside in the hydrocarbon interior, where charged and polar amino acids are almost never found. Charged residues are commonly seen at the lipid-water interface, but positively charged residues occur more often on the cytoplasmic face of transmembrane proteins. Transmembrane protein sequences and structures are adapted to the transition from water on one side of the membrane, to the hydrocarbon core of the membrane, and then to water on the other side of the membrane. The amino acids that constitute transmembrane segments reflect these transitions [4].

The amino acids Lys and Arg frequently have novel behaviours at the lipid–water interface. Both of these residues contain long aliphatic side chains with positively charged groups at the end. In many membrane proteins, there is an association between aliphatic chain of Lys or Arg and the hydrophobic portion of the bilayer, with the positively charged groups (amino or guanidinium) extending beyond to associate with negatively charged phosphate groups. This behavior, with the side chain pointing up out of the membrane core, has been termed snorkeling. If a Phe residue resides near the lipid–water interface, there will be a general arrangment of the residue with the aromatic ring oriented toward the membrane core. This is termed anti-snorkeling [4].

In addition, if proline residues are present, a transmembrane α-helix will be bent. Transmembrane α-helices often contain distortions and “kinks”—more so than for water-soluble proteins. Helix distortions may have evolved in membrane proteins because (1) helices, even distorted ones, are highly stable in the membrane environment, and (2) helix distortions may be one way to create structural diversity from the simple helix building blocks of most membrane proteins. About 60% of known membrane helix distortions are kinks at proline residues. Proline distorts the ideal α-helical geometry because of steric conflict with the preceding residue and because of the loss of a backbone H bond. Proline-induced kinks create weak points in the helix, which may facilitate movements required for transmembrane transport channels [4].

References

[1]. M, L.A. et al (2012). Principles of Biochemistry. 5th ed. New York: Pearson Education.

[2]. L, D.L. & C., M.m. (2011). Lehninger Principles of Biochemistry. 4th ed. New York: W.H. Freeman & Sumanas.

[3]. http://www.membranome.org/protein.php?pdbid=LAT_HUMAN

[4]. Garrette, L.H. & Grisham, C.M. (2008). Biochemistry. 4th ed. Belmont: Brooks Cole.

What amino acids are in transmembrane proteins?

What type of amino acid would you expect to find in the transmembrane portion of a membrane protein?

What does a transmembrane protein contain?

What proteins are also called transmembrane proteins?