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is highly consistent with idealized values (O/T = 0.137; O/R = 0.173 - see Fig.
6.16
for details), suggesting that complexation does not significantly distort the structure
of each monomer's hydrophobic core. We call this phenomenon
static complex-
ation
: since the hydrophobic core is not affected, the “fuzzy oil drop” model cannot
make accurate predictions regarding the complexation interface. Accordingly, cases
where the presence of an external protein molecule triggers significant deformations
in the protein's core (such as in 1G8M) are referred to as
dynamic complexation
.
This distinction provides a strong indication that complexation mechanisms may
take on many different forms. Active complexation appears to be an example of
chaperone-like activity (where the complementary molecule acts as the chaperone);
however in 2Q3A individual monomers evolve separately and develop a stable ter-
tiary structure which includes a well-ordered hydrophobic core.
The 1X21 protein, which is a fragment of a helix-hairpin-helix DNA binding
domain in a larger hydrolase molecule, does not constitute a functional group on its
own (Nishino et al.
2005
). Nevertheless, its structure exhibits a certain ordering of
hydrophobicity, approximating the idealized “fuzzy oil drop” model. For this pro-
tein, O/T = 0.143 while O/R = 0.177, indicating a situation similar to 2Q3A (where
the dimer emerges through static aggregation of two molecules without distorting
their respective cores). For this reason, analysis of the
Δ
H
pro fi le (i.e. its minima
and maxima) is not sufficient to identify the residues involved in complexation.
The 1DVZ protein (hormone/growth factor - human transthyretin in complex
with o-trifluoromethylphenyl antranilic acid) binds a potential drug which (according
to theoretical predictions) should help prevent the buildup of amyloidogenic plaque
(Klabunde et al.
2000
) . Analysis of its
Δ
H
profile suggests that the presence of a
ligand does not result in substantial structural changes in the transthyretin molecule;
however section 69-80 diverges from the theoretical optimum (in terms of hydro-
phobicity) and introduces an element of instability which may, in turn, destabilize
the entire molecule. Section 69-80 appears to be connected with the ability of tran-
sthyretin to attach additional molecules, facilitated by rapid structural changes.
While somewhat speculative, this conclusion is justified: studies suggests that
“divergent” sections frequently participate in complexation processes (Fig.
6.17
).
3SDH (cooperative dimeric hemoglobin from the blood clam
Scapharca inaequi-
valvis
) is another example of a protein where the “fuzzy oil drop” does not provide
sufficient data to pinpoint complexation sites (Royer
1994
). This protein has been
studied both in its unliganded (deoxy) and carbon monoxide (CO) liganded states.
In the case of 3SDH, the presence of a large ligand (heme) dominates the activity
of hemoglobin. Lys 96 and Phe 97 participate in two important processes: binding
heme and facilitating intersubunit communication. The “fuzzy oil drop” model cor-
rectly singles out these residues as belonging to a local hydrophobicity maximum.
Other residues which form the complexation interface are somewhat less pronounced
on the
Δ
H
graph - which is why the graph itself is not sufficient to accurately
model the complexation site. Figure
6.18
(top) also highlights Ile 114, Trp 135 and
Leu 138 (white spheres), which - despite being strongly hydrophobic - generate a
localized hydrophobicity deficiency, resulting from the relatively loose packing of
residues in their region and suggesting a potential interaction site.
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