Biomedical subjects

Alla Kirzhner

Publications and source records attributed to Alla Kirzhner.

3 recordsLinked to original sources

PubMed2003

Protein sequences yield a proteomic code.

Analysis of crystallized protein structures suggests that globular proteins are organized as consecutively connected units of 25-35 residues. These units are closed loops, that is returns of the polypeptide chain trajectory to a close contact with itself. This universal feature of apparently polymer-statistical nature is a basis for a principally novel view on the globular proteins as loop fold structures. The same unit size has been detected in protein sequences translated from complete prokaryotic genomes by positional autocorrelation analysis, which strongly indicates the evolutionary connection of the units. The units are further characterized by prototype sequences matching to their numerous derivatives in the translated genomes. The matches to five strongest prokaryotic prototypes and three prototypes of C. elegans are identified in the sequences of crystallized proteins, and their structures analyzed. Corresponding segments of the polypeptide chains in majority of cases form closed loops, though evolutionary fate of every prototype element is shown to be rather diverse. Then loop ends can be separated by a sequence-wise distant segments and stabilized by the spatial interactions in the context of the overall globular structure. The units belong to a presumably limited spectrum of the sequence prototypes, full repertoire of which would constitute a proteomic code.

Amino Acid Motifs↗

PubMed2003

Spelling protein structure.

Recent sequence analysis of complete prokaryotic proteomes suggests that in early evolutionary stages proteins were rather small, of the size 25-35 amino acids. Corroborating evidence comes from protein crystal data, which indicate this size for closed loops--universal structural units of globular proteins. In the latest development we were able to derive and structurally characterize several sequence/structure prototypes apparently representing early protein units. Structurally the prototypes appear as closed loops stabilized by end-to-end van der Waals interactions. While nearly standard in size the loops are highly diverse in terms of their secondary structure. A presentation of the protein as an assembly of descendants of the prototypes, the first of its kind, is described in detail here. The sequence and structure of the ATP-binding subunit of histidine permease of S. typhimurium is shown to contain several modified copies of different prototype elements, closed loops, and, thus, can be spelled as: x-PI-x-PIV-PVI-PII-PVII-x, where PI-PVII are the prototype elements. This study sets up the basic principles for the sequence/structure prototype spelling of globular proteins.

ATP-Binding Cassette Transporters↗

PubMed2002

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.

Amino Acid Motifs↗