Walden, H; Bell, Gs; Russell, Rjm; Siebers, B; Hensel, R; Taylor, Gl:

Tiny TIM: A small, tetrameric, hyperthermostable triosephosphate isomerase

In: JOURNAL OF MOLECULAR BIOLOGY, Jg. 306 (2001) ; Nr. 4, S. 745-757
ISSN: 0022-2836
Zeitschriftenaufsatz / Fach: Biologie
Abstract:
Comparative structural studies on proteins derived from organisms with growth optima ranging from 15 to 100 degreesC are beginning to shed light on the mechanisms of protein thermoadaptation. One means of sustaining hyperthermostability is for proteins to exist in higher oligomeric forms than their mesophilic homologues. Triosephosphate isomerase (TIM) is one of the most studied enzymes, whose fold represents one of nature's most common protein architectures. Most TIMs are dimers of approximately 250 amino acid residues per monomer. Here, we report the 2.7 Angstrom resolution crystal structure of the extremely thermostable TIM from Pyrococcus woesei, a hyperthermophilic archaeon growing optimally at 100 degreesC, representing the first archaeal TIM structure. P. woesei TIM exists as a tetramer comprising monomers of only 228 amino acid residues. Structural comparisons with other less thermostable TIMs show that although the central P-barrel is largely conserved, severe pruning of several helices and truncation of some loops give rise to a much more compact monomer in the small hyperthermophilic TIM. The classical TIM dimer formation is conserved in P. woesei TIM. The extreme thermostability of PwTIM appears to be achieved by the creation of a compact tetramer where two classical TIM dimers interact via an extensive hydrophobic interface. The tetramer is formed through largely hydrophobic interactions between some of the pruned helical regions. The equivalent helical regions in less thermostable dimeric TIMs represent regions of high average temperature factor. The PwTIM seems to have removed these regions of potential instability in the formation of the tetramer. This study of PwTIM provides further support for the role of higher oligomerisation states in extreme thermal stabilisation. (C) 2001 Academic Press.

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