PSI-BLAST searches using hidden Markov models of structural repeats: prediction of an unusual sliding DNA clamp and of beta-propellers in UV-damaged DNA-binding protein

Neuwald, A. F., Poleksic, A. (September 2000) PSI-BLAST searches using hidden Markov models of structural repeats: prediction of an unusual sliding DNA clamp and of beta-propellers in UV-damaged DNA-binding protein. Nucleic Acids Research, 28 (18). pp. 3570-3580. ISSN 0305-1048

URL: http://www.ncbi.nlm.nih.gov/pubmed/10982878
DOI: 10.1093/nar/28.18.3570

Abstract

We have designed hidden Markov models (HMMs) of structurally conserved repeats that, based on pairwise comparisons; are unconserved at the sequence level, To model secondary structure features these HMMs assign higher probabilities of transition to insert or delete states within sequence regions predicted to form loops, HMMs were optimized using a sampling procedure based on the degree of statistical uncertainty associated with parameter estimates, A PSI-BLAST search initialized using a checkpoint-recovered profile derived from simulated sequences emitted by such a HMM can reveal distant structural relationships with, in certain instances, substantially greater sensitivity than a normal PSI-BLAST search. This is illustrated using two examples involving DNA- and RNA-associated proteins with structurally conserved repeats. In the first example a putative sliding DNA clamp protein was detected in the thermophilic bacterium Thermotoga maritima, This protein appears to have arisen by way of a duplicated beta-clamp gene that then acquired features of a PCNA-like clamp, perhaps to perform a PCNA-related function in association with one or more of the many archaeal-like proteins present in this organism. In the second example, beta-propeller domains were predicted in the large:subunit of UV-damaged DNA-binding protein and in related proteins, including the large subunit of cleavage-polyadenylation specificity factor, the yeast Rse1p land human SAP130 pre-mRNA splicing factors and the fission yeast Rik1p gene silencing protein.

Item Type: Paper
Uncontrolled Keywords: PIGMENTOSUM GROUP-E ASSEMBLY FACTOR-I POLYMERASE-III HOLOENZYME ESCHERICHIA-COLI FISSION YEAST WD-REPEAT REPAIR DEFECT CELL-CYCLE SEQUENCE ALIGNMENT
Subjects: bioinformatics
bioinformatics > genomics and proteomics
bioinformatics > computational biology
bioinformatics > genomics and proteomics > computers > computer hardware
bioinformatics > genomics and proteomics > computers > computer software
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > DNA binding protein
CSHL Authors:
Communities: CSHL labs > Neuwald lab
Depositing User: Matt Covey
Date: September 2000
Date Deposited: 28 Jan 2014 20:02
Last Modified: 28 Jan 2014 20:02
PMCID: PMC110734
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29438

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