The role of semidisorder in temperature adaptation of bacterial FlgM proteins

Abstract

Probabilities of disorder for FlgM proteins of 39 species whose optimal growth temperature ranges from 273 K (0°C) to 368 K (95°C) were predicted by a newly developed method called Sequence-based Prediction with Integrated NEural networks for Disorder (SPINE-D). We showed that the temperature-dependent behavior of FlgM proteins could be separated into two subgroups according to their sequence lengths. Only shorter sequences evolved to adapt to high temperatures (>318 K or 45°C). Their ability to adapt to high temperatures was achieved through a transition from a fully disordered state with little secondary structure to a semidisordered state with high predicted helical probability at the N-terminal region. The predicted results are consistent with available experimental data. An analysis of all orthologous protein families in 39 species suggests that such a transition from a fully disordered state to semidisordered and/or ordered states is one of the strategies employed by nature for adaptation to high temperatures.

Figure 1

Predicted disorder probability as a function of residue indices according to the multiple-sequence alignment shown in the top panel (red indicates highly conserved regions). The defined semidisordered area (0.4–0.7 in disorder probability) is in gray. To see this figure in color, go online.

Figure 2

(A and B) As in Figure 1, but for two subgroups of proteins with different lengths (>97 for A and ≤97 for B). These two subgroups of proteins have distinctly different temperature-dependent disordered probabilities. The defined semidisordered area (0.4–0.7 in disorder probability) is in gray. To see this figure in color, go online.

Figure 3

Average disorder probability for the N-terminal region (up to aligned position 56) as a function of the optimal growth temperature for proteins from subgroup A (open circles) and subgroup B (solid circles).

Figure 4

Evolution tree (blue, subgroup A; red, subgroup B). To see this figure in color, go online.

Figure 5

Average predicted helical probability as a function of optimal growth temperature for the N-terminal and structured regions of FlgM of subgroups A and B, respectively. Correlation coefficients are 0.08 for subgroup A (N-terminal) and 0.55 for subgroup B (N-terminal).

Figure 6

Predicted disorder probability (top) and helical probability (bottom) for thermophilic FlgM1 (A. aeolicus in red) and mesophilic FlgM19 (S. typhimurium in blue). Experimentally determined helical regions for FlgM1 in complex with sigma-28 (PDB ID 1SC5, chain B) are shown on the x axis with red labels. To see this figure in color, go online.

Figure 7

(A) Distribution of correlation coefficients between the disordered probabilities and temperature. The dotted line highlights the overall negative correlation observed for the majority of protein families. (B) Average disorder probability of ATP-dependent RNA helicases in each species along with its optimal growth temperature. The dotted line is the regression line with a correlation coefficient of −0.69. The defined semidisordered area (disorder probability of 0.4–0.7) is in gray.