Python Programming for Biology: Bioinformatics and Beyond

Figure 15.2 (Plate 1).  The general form of transmembrane proteins that reside in a

lipid bilayer. Transmembrane proteins are embedded within the plane of a hydrophobic

cellular membrane, which is composed of a double layer of lipid molecules and other

membrane proteins. In contrast to aqueous proteins that reside in water, a membrane

protein adopts a structure so that its hydrophobic (water-hating) parts lie within the

membrane, often with hydrophilic (water-loving) parts protruding into the aqueous regions

either side of the membrane. There are two common types of structure that transmembrane

proteins adopt to form a hydrophobic membrane domain: an α-helical bundle or a β-barrel.

Within  a  membrane  the  polypeptide  backbone  of  a  protein  forms  regular  hydrogen

bonds with itself. Indeed, there is no water to interact with in any case. And because the

domain  crosses  the  membrane,  only  interacting  with  the  aqueous  environment  at  the

edges,  there  are  only  two  basic  ways  that  a  protein  can  pack  into  a  compact,  functional

shape.  The  most  common  of  these  is  the  alpha-helical  bundle,  where  the  rods  of  the

helices  (i.e.  the  hydrogen-bonded  secondary-structure  part)  cut  across  the  plane  of  the

membrane and lie roughly parallel with one another. The other transmembrane form is the

beta-barrel, where a beta-sheet secondary structure zigzags its way across the width of the

membrane, each strand hydrogen-bonding with the next to eventually form a closed ring.

Although  these  structural  strategies  are  different  they  have  a  similarity  in  that  they  both

present  a  very  hydrophobic  surface  of  amino  acid  side  chains,  to  remain  stable  in  the

membrane. The inside of such folds is pretty hydrophobic too, otherwise they would tend

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to  migrate  to  the  water  surface.  Overall,  transmembrane  structures  are  notably  different

from  the  aqueous  proteins,  and  they  are  important  to  consider  because  they  are  quite

common;  about  30%  of  all  proteins  have  a  transmembrane  domain.  Unfortunately,

however, you will see proportionately few three-dimensional structures for them, because

they  are  notoriously  difficult  to  do  the  normal  experiments  with,  given  their  need  to  be

surrounded by lipids (or similar).