Closed loops: persistence of the protein chain returns.
It has recently been discovered that globular proteins are universally built from standard loop-n-lock units of about 30 amino acid residues. The hypothesis has been put forward on the loop stage in the protein evolution when the units were autonomous. Later they joined together making longer chains. One would expect that the early individual loop-n-lock elements might still be detected in modern protein sequences as remnants of the hypothetical 30-residue sequence prototypes. Among several strong sequence motifs, extracted from protein sequences of 23 complete bacterial proteomes, one 32-residue prototype was studied here in detail. Numerous sequence segments related to the prototype are identified in the crystal structures of proteins of a PDB_SELECT database. Analysis of the respective chain trajectories for the cases with different degrees of sequence conservation confirms that the majority of the segments correspond to the closed loops. In the evolutionary diversification of the prototypes the secondary structure yields first, while the sequence is still moderately conserved. The last feature to go is the chain return property. Apparently, the opening of the loops would severely destabilize the protein fold, which explains their conservation.
Berezovsky
Igor N
IN
Department of Structural Biology, The Weizmann Institute of Science, POB 26, Rehovot 76100, Israel. igor.berezovsky@weizmann.ac.il
Kirzhner
Valery M
VM
Kirzhner
Alla
A
Rosenfeld
Vladimir R
VR
Trifonov
Edward N
EN
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein
D011506:Proteins