Correlation between Al³⁺-induced thermal stability and inhibition of fibrillation of N-terminal domain of the hydrogenase maturation factor.

Fibrillation can be induced in proteins by altering solvent conditions. Stabilization of the protofibrillar structure arrests formation of longer fibers. Thermal stability and fibrillation of N-terminal domain of the hydrogenase maturation factor (HypF-N) were studied in the presence of a series of metal ions. Only Al3+ was able to reverse the thermal denaturation of HypF-N upon heating. On being exposed to denaturing conditions, the native protein formed fibrillar structure under moderately denaturing conditions, whereas in the presence of Al3+, the protein was found to retain its native conformation. Under strongly denaturing conditions, only Al3+ was able to stabilize the protein in the fibrillar state. Spectrofluorimetric analysis revealed that Al3+ alone was able to stabilize the partially unfolded intermediate state of HypF-N. Based on the similarity in observations, we propose a link between reversal of thermal instability of HypF-N and its ability to form an intermediate structure in the presence of Al3+. Al3+ stabilizes the partially unfolded state in the N↔I↔U equilibrium so that upon heating, the three-dimensional structure of the protein is not lost completely. Kinetic analysis confirmed that Al3+ interacts with an early structure on the aggregation landscape and delays fibrillation. Under mildly denaturing state, HypF-N is able to recover its native conformation in the presence of Al3+ and under strongly denaturing conditions, the protein does not acquire a completely disordered structure. Instead, it forms an ordered β-sheet-rich structure. © 2013 BioFactors, 39(6):597-607, 2013 [ABSTRACT FROM AUTHOR]