A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3.

TitleA proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3.
Publication TypeJournal Article
Year of Publication2008
AuthorsYu EYoung, Wang F, Lei M, Lue NF
JournalNat Struct Mol Biol
Volume15
Issue9
Pagination985-9
Date Published2008 Sep
ISSN1545-9993
KeywordsAmino Acid Sequence, Base Sequence, Candida albicans, DNA, Fungal, Fungal Proteins, Genes, Fungal, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Phenotype, Protein Folding, Protein Interaction Domains and Motifs, Recombinant Proteins, Sequence Homology, Amino Acid, Telomerase, Telomere-Binding Proteins
Abstract

Ever shorter telomeres 3 (Est3) is an essential telomerase regulatory subunit thought to be unique to budding yeasts. Here we use multiple sequence alignment and hidden Markov model-hidden Markov model (HMM-HMM) comparison to uncover potential similarities between Est3 and the mammalian telomeric protein Tpp1. Analysis of site-specific mutants of Candida albicans Est3 revealed functional distinctions between residues that are conserved between Est3 and Tpp1 and those that are unique to Est3. Although both types of residues are important for telomere maintenance in vivo, only the former contributes to telomerase activity in vitro and facilitates the association of Est3 with telomerase core components. Consistent with a function in protein-protein interaction, the residues common to Est3 and Tpp1 map to one face of an OB-fold model structure, away from the canonical nucleic acid binding surface. We propose that Est3 and the OB-fold domain of Tpp1 mediate a conserved function in telomerase regulation.

DOI10.1038/nsmb.1471
Alternate JournalNat Struct Mol Biol
PubMed ID19172753
PubMed Central IDPMC2656765
Grant ListGM069507 / GM / NIGMS NIH HHS / United States
R01 GM069507-04 / GM / NIGMS NIH HHS / United States
R01 GM083015 / GM / NIGMS NIH HHS / United States
GM083015 / GM / NIGMS NIH HHS / United States
R01 GM069507 / GM / NIGMS NIH HHS / United States
R01 GM083015-01 / GM / NIGMS NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587