Abiotic Stress Adaptation: Protein Folding Stability and Dynamics - Abiotic Stress: Plant Responses and Applications in Agriculture - page 5

2. Protein folding and abiotic stress
A striking feature of protein folding is that the overall mechanism follows simple physical
rules, but examination in finer detail reveals a much greater complexity [8]. The protein
structure-function paradigm has been reassessed with the discovery of partially unfolded or
intrinsically disordered proteins that are fully functional. These proteins are widely distrib‐
uted in eukaryotes and fulfill crucial biological functions like transcriptional regulation, sig‐
nal transduction [9], enzyme catalysis and protein ligand interactions. They contain native-
like secondary structure elements but lack the tertiary interactions of folded proteins. One
has to keep in mind that protein function is protected by stabilization of well-defined struc‐
tural regions but is largely dependent on protein motion and dynamics. NMR dynamic ex‐
periments indicate that protein conformational exchange spans a variety of time scales
ranging from picoseconds to milliseconds [10]. Complete description of protein function,
that may involve motion, requires an understanding of the molecular dynamics [11]. Many
proteins form partially folded intermediate states along their folding-pathway. To search for
correlations between function, structure and dynamics, it is essential to include all states
formed at equilibrium [12, 13] in order to characterize protein dynamics under unfavorable
environmental conditions.
Protein conformations and interconversion between different states are largely modified by
internal and external signals such as ligand binding, phosphorylation or cleavage, molecular
recognition or environmental changes [14]. In vivo , protein folding occurs spontaneously,
meaning that proteins permanently exchange between folded, partially folded, locally un‐
folded and unfolded states during the period from protein synthesis until their degradation.
According to the energy landscape theory, the free energy barriers connecting these states
are small [15], suggesting that minor perturbations in vivo can have significant effects on the
populations of different states and hence protein function. Intermolecular forces that drive
protein folding generally stabilize both folded and unfolded states, but an altered balance in
these forces can result in aggregation or misfolding to non-functional proteins [16]. Protein
unfolding, misfolding and aggregation are a common threat to the living cell, especially
when undergoing abiotic stress. To cope with stress, plants have developed various mecha‐
nisms to facilitate protein folding and to suppress protein misfolding.
3. Stability versus flexibility - How to protect protein function?
Stabilizing proteins in their functional conformation is one of the great challenges in plant
stress metabolism. Stress induced alterations in the structural and energy landscape of pro‐
teins affect and may inhibit both protein-ligand and protein-protein interactions. Small mol‐
ecules typically bind proteins in small cavities, whereas proteins recognize large surface
areas [17]. Thus, protein function is a balancing act between structural stability and the con‐
formational flexibility needed for protein function. Protein stability results from stabilizing
and destabilizing interactions of the polypeptide chains that slightly favor the folded state as
compared to partially folded or unfolded states under physiological conditions (Figure 2).