Page 172 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN013D-616 July 27, 2001 12:5

212 Protein Structure

loops is enormously variable, whereas the length of the These are known as αβ folds. In more complex folds mul-
β-strands are similar in all enzymes. tiple layers of sheet and additional layers of helices have
been observed to give rise to αββ (as in ribonuclease) and
2. Open β-Sheets αββα folds (as in glutamine phosphribosyl pyrophosphate
amidotransferase N-terminal domain).
The second class of proteins in the α/β family of folds
contains a large open sheet formed from mostly parallel
β-strands with helices on both sides. In contrast to the I. Small Proteins, Unusual Folds
TIM barrel there are fewer limitations on the number of There are a substantial number of small proteins that defy
strands within the sheet and may vary from 4 to 10. The
classification into one of the groups listed above. Some
first example of this type of fold was seen in lactate dehy-
of these have limited regular secondary structure whereas
drogenase which contains a motif that is widely observed
others are stabilized by metal ligands, cofactors, or disul-
in dinucleotide binding proteins (this motif is often re-
fidebonds.Examplesofthesefoldsincludethezinc–finger
ferred to as the Rossmann fold) and was the first example
DNA binding motifs, many small iron–sulfur proteins,
of a domain superfamily (Fig. 14b). The observation of
toxins and protein-inhibitors (Fig. 16).
a common fold in the dehydrogenases by Rossmann and
coworkers started the entire field of structural comparison
and study of structural evolution. VIII. MEMBRANE PROTEINS
All of the connections between β-strands are formed by
right-handed crossovers. As a consequence, the strand or-
Approximately one third of all proteins are tightly asso-
der within the sheet must reverse in order to place helices
ciated with membranes. These are much more difficult
on both sides of the sheet (Note: the consecutive strand
to crystallize or study by NMR than water-soluble pro-
order in the (α/β) 8 barrel places the α-helices on one side
teins. As a consequence, there are far fewer structures of
of the sheet). In the classical Rossmann fold, which con- membrane proteins. Even so, those that have been deter-
tains six β-strands, the N-terminal strand in the fold is mined provide insight into the manner in which polypep-
located adjacent to the center of the motif. The first two tide chains interact with lipid bilayers.
α-helices lie on one side of the sheet as the first three Membrane proteins fall into two classes: peripheral and
strands are added. Thereafter the chain returns to the cen- integral.Peripheralmembraneproteinsareassociatedwith
ter of the sheet and adds the next three strands with the the membrane, but may be removed by high concentra-
reverse strand order such that the subsequent helices are tions of salt or metal chelators such as EDTA. In most as-
added on the opposite side of the sheet. pects the structures of peripheral membrane proteins are
There are many varieties of open sheet α/β proteins
very similar to water-soluble proteins. Integral membrane
which include differing numbers of strands, connections
proteins differ in that they are very difficult to extract from
between strands that are not adjacent and incorporation of
the lipid bilayer and require detergents for solubilization.
antiparallel strands. In most cases the ligand binding sites
Detergents disrupt the lipid bilayer and bind to the hy-
arelocatedattheC-terminalendsofthe β-strandsandlieat
drophobic surfaces of the protein that are buried within
the crevice at the edge of the sheet where the strand order is
the membrane.
reversed. The loops that connect the strands to the helices
Integral membrane proteins all share the common prob-
typically provide the residues necessary for specificity.
lem of inserting a polypeptide chain into the hydrophobic
The size of the connecting loops are enormously variable
interior of the lipid bilayer. This poses a thermodynamic
in α/β proteins.
problem on account of the hydrogen bonding propensity
of the polypeptide chain. Clearly any segment of the pro-
tein that passes through the lipid bilayer must accommo-
H. α + + β Proteins
date the hydrogen bonding potential of the polypeptide
The α + β class of proteins is highly variable, indeed chain. Originally it was believed that an α-helix would be
over a hundred distinct folds have been observed in this the only secondary structural element to pass through the
group. Members of this class typically contain one or more lipid bilayer since it alone fulfills the hydrogen bonding
β-sheets which have a bias toward antiparallel connec- capacity of the polypeptide chain in a consecutive man-
tions. As such the α-helical and β-sheet regions tend to ner. Indeed the α-helix is the only way to pass a single
be segregated along their sequences. Several examples of transmembrane segment of protein through a membrane.
proteins that fall in this class are shown in Fig. 15. In the However, although a large number of membrane proteins
simplest cases the helices lie on one side of the sheet which areformedfromα-helicalbundlesasignificantnumberare
maybecomparativelyflatorsteeplycurvedasinubiquitin. built from β-strands. Both of these strategies for building