STRUCTURAL FEATURES CORRELATED WITH THE EXTREME THERMOSTABILITY OF 1[4FE-4S] FERREDOXIN FROM THE HYPERTHERMOPHILIC BACTERIUM THERMOTOGA-MARITIMA

Understanding the molecular mechanisms behind extreme temperature stab ility is of relevance for the protein folding problem and for designin g proteins for industrial and medical applications. A powerful approac h for understanding the structural basis of thermostability is the com parison of high resolution structures of homologous proteins from meso philes and thermophiles. The 1.75 Angstrom crystal structure of Thermo toga maritima 1[4Fe-4S] ferredoxin was compared with those of mesophil ic ferredoxins. Detailed analysis of structural differences reveals th at thermostability is achieved without large changes of the overall po lypeptide chain folding. The most striking differences include the for mation of additional hydrogen bonding networks involving both side-cha in and main-chain atoms. These networks are mainly connecting turns an d strongly fix the N-terminus to the central core of the protein, incr easing the overall rigidity of Thermotoga maritima ferredoxin. Other p ossibly stabilizing factors are the shortening of a solvent exposed su rface loop, the increased content of alanines in the second cu-helix, and the replacement of three residues close to the iron-sulfur cluster , which are in energetically unfavourable conformations in other ferre doxins, by glycines.