Using motif-based methods in multiple genome analyses: a case study comparing orthologous mesophilic and thermophilic proteins.
Protein motifs represent highly conserved regions within protein families and are generally accepted to describe critical regions required for protein stability and/or function. In this comprehensive analysis, we present a robust, unique approach to identify and compare corresponding mesophilic and thermophilic sequence motifs between all orthologous proteins within 44 microbial genomes. Motif similarity is determined through global sequence alignment of mesophilic and thermophilic motif pairs, which are identified by a greedy algorithm. Our results reveal only modest correlation between motif and overall sequence similarity, highlighting the rationale of motif-based approaches in comprehensive multigenome comparisons. Conserved mutations reflect previously suggested physiochemical principles for conferring thermostability. Additionally, comparisons between corresponding mesophilic and thermophilic motif pairs provide key biochemical insights related to thermostability and can be used to test the evolutionary robustness of individual structural comparisons. We demonstrate the ability of our unique approach to provide key insights in two examples: the TATA-box binding protein and glutamate dehydrogenase families. In the latter example, conserved mutations hint at novel origins leading to structural stability differences within the hexamer structures. Additionally, we present amino acid composition data and average protein length comparisons for all 44 microbial genomes.
La
David
D
Department of Chemistry, California State Polytechnic University at Pomona, 3801 West Temple Avenue, Pomona, California 91768, USA.
Silver
Melanie
M
Edgar
Robert C
RC
Livesay
Dennis R
DR
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D020745:Genome, Archaeal; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009154:Mutation; D040901:Proteomics / Q000379:methods* / Q000706:statistics & numerical data; D017386:Sequence Homology, Amino Acid; D013696:Temperature
D019843:Archaeal Proteins; D001426:Bacterial Proteins