Bioinformatics of Myelin Membrane Proteins - Molecules: Nucleation, Aggregation and Crystallization - page 39

-helical membrane proteins, methods such as TMHMM (a
method for prediction of transmembrane helices based on a hidden
Markov model; Krogh et al ., 2001), prodiv-TMHMM (Viklund, Elofsson,
2004), HMMTOP (Tusnády, Simon, 2001) and MEMSAT (Jones, 2007)
are among the best choices for topology predictions. Recently, we have
developed an experimentally based algorithm called the “

For α

G predictor,”
which predicts, from the amino acid sequence of a protein, the Gibbs' free
energy of membrane insertion for transmembrane

∆

-helices (Hessa et al .,
2007). This last predictor is the one used below in the analysis of the
myelin membrane proteins.
Some membrane proteins have N-terminal, cleavable signal peptides
that guide them to the endoplasmic reticulum membrane. Signal peptides
are on the order of 10-20 residues long and have a three-partite structure:
a short N-terminal region (n-region) including one or two basic residues,
a central hydrophobic region (h-region), and a more polar C-terminal
region (c-region) that is 4-7 residues long and is recognized by the signal
peptidase enzyme. The signal peptidase cleavage site is defined by small
residues in positions

α

− 1 and − 3 relative to the cleavage site [the so-called

( 3)-rule]. Signal peptides can be reliably identified using the SignalP

predictor (Dyrløv-Bendtsen, 2004), which scores the typical signal peptide
n-, h- and c-regions. SignalP is used below in the analysis of the myelin
proteins.
Many other prediction methods based on the primary structure of pro-
teins are available (www.expasy.ch/tools). One basic assumption of these
methods is that structurally similar proteins are similar in their function
(Aloy et al ., 2005, 2006). Prediction of protein-protein interactions based
on structural information is still far from perfect, but allows in some cases
the production of structural models at exceptionally high resolution
(Kiel et al ., 2005).

− 1, −

Focus on the Myelin Membrane

The last report analyzing the structure and function of the myelin proteins
from primary sequence data was published more than a decade ago