Biology Reference
In-Depth Information
Amino Acid
Sequence
Protein Folds
=
Rate of
Translation
Micro-Environment
(
Mechanisms
)
Fig. 11.2 A triadic model of protein folding inside the cell. According to this model, protein folds
with a theory of biological evolution (in the form of say a cell model). One such
biological theory is the “information-energy” landscape theory outlined here, which
can be viewed as another manifestation of the
information-energy complementarity
principle
presented in Sect.
2.3.2
.
There are two contrasting views on the genotype-phenotype relation in protein
folding: (a) the so-called Anfinsen's dogma that a protein's 3-D structure is
completely determined by its amino acid sequence (but see Sect.
6.1.1
) and (b)
the opposite view that genotype has no
predictable
influence on three-dimensional
protein folds. Belonging to the latter group is the
translation-dependent folding
(TDF) hypothesis recently proposed by Newman and Bhat (2007), according to
which the differences in the rates of the translation of the mRNAs on the ribosomes
can lead to different protein folds. In contrast to the TDF hypothesis of Newman
and Bhat, Anfinsen's dogma may be referred to as the
sequence-dependent folding
(SDF) hypothesis. Although I support TDF hypothesis, it is deemed unnecessary to
view the SDF hypothesis as completely irrelevant. Rather it appears to me that both
SDF and TDF hypotheses are needed to formulate a coherent molecular theory of
protein folding. One such effort is shown below which utilizes the definition of the
are determined by their folds, i.e., molecular shapes (Ji and Ciobanu 2003).
Workers in the field of protein folding have tended to think in term of thermo-
dynamic principles only as exemplified by the
energy landscape model
of protein
folding (see above) but Newman and Bhat (2007) suggest an alternative approach
and emphasize the role of kinetics as being dominant in protein folding. As
indicated in Fig.
11.2
, I advocate a third view, the view that protein folding is an
example of dissipative structure encompassing the following three irreducible
elements:
1. Amino acid sequence (or the nucleotide sequence of mRNA)
2. Thermodynamic and kinetic factors determining the rates of translation of
mRNA on the ribosome
3. Microenvironmental factors inside the cell that select a subset of translation rates
compatible with the needs of the cell
It may be that these three aspects are inseparably “fused” together in the
