Identification of functionally important domains in the N-terminal region of telomerase reverse transcriptase.

TitleIdentification of functionally important domains in the N-terminal region of telomerase reverse transcriptase.
Publication TypeJournal Article
Year of Publication2000
AuthorsXia J, Peng Y, Mian IS, Lue NF
JournalMol Cell Biol
Date Published2000 Jul
KeywordsAmino Acid Sequence, Base Sequence, Binding Sites, Conserved Sequence, DNA-Binding Proteins, Endopeptidases, Enzyme Stability, Molecular Sequence Data, Mutation, Nucleic Acids, RNA, Sequence Homology, Amino Acid, Telomerase

Telomerase is a ribonucleoprotein reverse transcriptase responsible for the maintenance of one strand of telomere terminal repeats. The key protein subunit of the telomerase complex, known as TERT, possesses reverse transcriptase-like motifs that presumably mediate catalysis. These motifs are located in the C-terminal region of the polypeptide. Hidden Markov model-based sequence analysis revealed in the N-terminal region of all TERTs the presence of four conserved motifs, named GQ, CP, QFP, and T. Point mutation analysis of conserved residues confirmed the functional importance of the GQ motif. In addition, the distinct phenotypes of the GQ mutants suggest that this motif may play at least two distinct functions in telomere maintenance. Deletion analysis indicates that even the most N-terminal nonconserved region of yeast TERT (N region) is required for telomerase function. This N region exhibits a nonspecific nucleic acid binding activity that probably reflects an important physiologic function. Expression studies of various portions of the yeast TERT in Escherichia coli suggest that the N region and the GQ motif together may constitute a stable domain. We propose that all TERTs may have a bipartite organization, with an N-GQ domain connected to the other motifs through a flexible linker.

Alternate JournalMol Cell Biol
PubMed ID10866675
PubMed Central IDPMC85968

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