Fold conservation

Surface features are not strictly dependent on sequence or fold conservation. Experimentally determined surface features from a certain structure can be used to search and detect matching sites on the surfaces of unrelated proteins without function assignment. This can be accomplished using methods such as SiteEngine [205]. Other tools that can be used for the analysis of protein surfaces are Surface, GRASS [206], and SURFNET [207],... 

Shakhnovich E I, Abkevich V and Ptitsyn O 1996 Conserved residues and the mechanism of protein folding Nature 379 96-8... 

The globin fold has been used to study evolutionary constraints for maintaining structure and function. Evolutionary divergence is primarily constrained by conservation of the hydrophobicity of buried residues. In contrast, neither conserved sequence nor size-compensatory mutations in the hydrophobic core are important. Proteins adapt to mutations in buried residues by small changes of overall structure that in the globins involve movements of entire helices relative to each other. 

FIGURE 12.39 The proposed secondary structure for E. coli 16S rRNA, based on comparative sequence analysis in which the folding pattern is assumed to be conserved across different species. The molecule can be subdivided into four domains—I, II, III, and IV—on the basis of contiguous stretches of the chain that are closed by long-range base-pairing interactions. I, the 5 -domain, includes nucleotides 27 through 556. II, the central domain, runs from nucleotide 564 to 912. Two domains comprise the 3 -end of the molecule. Ill, the major one, comprises nucleotides 923 to 1391. IV, the 3 -terminal domain, covers residues 1392 to 1541. 

If a phylogenetic comparison is made of the 16S-Iike rRNAs from an archae-bacterium Halobacterium volcanii), a eubacterium E. coli), and a eukaryote (the yeast Saccharomyces cerevisiae), a striking similarity in secondary structure emerges (Figure 12.40). Remarkably, these secondary structures are similar despite the fact that the nucleotide sequences of these rRNAs themselves exhibit a low degree of similarity. Apparently, evolution is acting at the level of rRNA secondary structure, not rRNA nucleotide sequence. Similar conserved folding patterns are seen for the 23S-Iike and 5S-Iike rRNAs that reside in the... 

Conserved sequences that fold into large loops stabilized by three disulfide linkages. The name Kringle comes from the Scandinavian pastry that these structures resemble. They can mediate certain protein-protein interactions. 

Similar residues in the cores of protein structures especially hydrophobic residues at the same positions, are responsible for common folds of homologous proteins. Certain sequence profiles of conserved residue successions have been identified which give rise to a common fold of protein domains. They are organized in the smart database (simple modular architecture research tool) http //smait.embl-heidelberg.de. 

Sequence conservation is, in general, much weaker than structural conservation. There are proteins, which are clearly not related in sequence but are closely related in 3D-stmcture and fold, like heamoglobin and myoglobin, which have similar functions. In many proteins, fold elements like 4-helical bundles are repeated. Classifications of known structural folds of proteins are organized in the SCOP or CATH database see e.g., http //scop.mrc-lmb.cam.ac.uk/scop/. 

The universal antibiotic pactamycin targets a highly conserved region of 16S rRNA, contacting the tips of helices 23b and 24a in the central domain. Pactamycin folds up to mimic a RNA dinucleotide in that its... 

The Sema domain consisting of about 500 amino acids is characterized by highly conserved cysteine residues that form intramolecular disulfide bonds. Crystal structures have revealed that the Sema domain folds in the manner of the (3 propeller topology which is also found in integrins or the low-density lipoprotein (LDL) receptors. Sema domains are found in semaphorins, plexins and in the receptor tyrosine kinases Met and Ron. 

SNAREs is an acronym for soluble NSF acceptor protein receptors. They are a superfamily of small and mostly membrane-bound proteins that are distinguished by the presence of a conserved stretch of 60 amino acids referred to as a SNARE motif. With few exceptions, a single transmembrane domain is located adjacent to the SNARE motif at the C-terminal end. Many SNAREs possess in addition an independently folded N-terminal domain whose structures are more diverse. 

Small tfbiquitin-like modifier represents a family of evolutionary conserved proteins that are distantly related in amino-acid sequence to ubiquitin, but share the same structural folding with ubiquitin proteins. SUMO proteins are covalently conjugated to protein substrates by an isopeptide bond through their carboxyl termini. SUMO addition to lysine residues of target proteins, termed SUMOylation, mediates post-transla-tional modification and requires a set of enzymes that are distinct from those that act on ubiquitin. SUMOylation regulates the activity of a variety of tar get proteins including transcription factors. 

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