An Alternative Model of Amino Acid Replacement

The observed correlations between pairs of homologous protein sequences are typically explained in terms of a Markovian dynamic of amino acid substitution. This model assumes that every location on the protein sequence has the same background distribution of amino acids, an assumption that is incompatible with the observed heterogeneity of protein amino acid profiles and with the success of profile multiple sequence alignment. We propose an alternative model of amino acid replacement during protein evolution based upon the assumption that the variation of the amino acid background distribution from one residue to the next is sufficient to explain the observed sequence correlations of homologs. The resulting dynamical model of independent replacements drawn from heterogeneous backgrounds is simple and consistent, and provides a unified homology match score for sequence-sequence, sequence-profile and profile-profile alignment.Comment: Minor improvements. Added figure and reference

Structure, Organization, and Expression of the lct Gene for Lacticin 481, a Novel Lantibiotic Produced by Lactococcus lactis

The structural gene for the lactococcal lantibiotic lacticin 481 (lct) has been identified and cloned using a degenerated 20-mer DNA oligonucleotide based on the amino-terminal 7 amino acid residues of the purified protein. The transcription of the lct gene was analyzed, and its promoter was mapped. DNA sequence analysis of the lct gene revealed an open reading frame encoding a peptide of 51 amino acids. Comparison of its deduced amino acid sequence with the amino-terminal sequence and the amino acid composition of lacticin 481 indicates that the 61-residue peptide is prelacticin 481, containing a 27-residue carboxyl-terminal propeptide and a 24-residue amino-terminal leader peptide which lacks the properties of a typical signal sequence and which is significantly different from the leaders of other lantibiotics. The predicted amino acid sequence of prolacticin 481 contains 3 cysteines, 2 serines, and 2 threonines which were not detectable in amino acid analyses of mature lacticin 481. Based on these results and on characterization by two-dimensional NMR techniques, a structural model is proposed in which 2 cysteine residues are involved in lanthionine and one in β-methyllanthionine formation, and a 4th threonine residue is dehydrated. This model predicts a molecular mass for lacticin 481 of 2,901, which is in excellent agreement with that obtained from mass spectrometry.

Amino acid metabolism conflicts with protein diversity

The twenty protein coding amino acids are found in proteomes with different relative abundances. The most abundant amino acid, leucine, is nearly an order of magnitude more prevalent than the least abundant amino acid, cysteine. Amino acid metabolic costs differ similarly, constraining their incorporation into proteins. On the other hand, sequence diversity is necessary for protein folding, function and evolution. Here we present a simple model for a cost-diversity trade-off postulating that natural proteomes minimize amino acid metabolic flux while maximizing sequence entropy. The model explains the relative abundances of amino acids across a diverse set of proteomes. We found that the data is remarkably well explained when the cost function accounts for amino acid chemical decay. More than one hundred proteomes reach comparable solutions to the trade-off by different combinations of cost and diversity. Quantifying the interplay between proteome size and entropy shows that proteomes can get optimally large and diverse

Molecular cloning and sequence analysis of the cDNA encoding the human acrosin-trypsin inhibitor (HUSI-II)

A complete cDNA clone encoding the human acrosin-trypsin inhibitor HUSI-II has been isolated from a cDNA library of human testis and completely sequenced. The cDNA of 594 bp contained an open reading frame of 252 base pairs, The deduced amino acid sequence comprised the complete amino acid sequence of HUSI-II[1] and a putative signal peptide. Northern blotting analysis revealed that HUSI-II is synthesized in testis, epididymis and seminal vesicle, but not in the prostate gland

A FAMILY OF CATION ATPASE-LIKE MOLECULES FROM PLASMODIUM-FALCIPARUM

Abstract. We report the nucleotide and derived amino acid sequence of the ATPase 1 gene from Plasmodium falciparum. The amino acid sequence shares homology with the family of "P-type cation transloeating ATPases in conserved regions important for nucleotide binding, conformational change, or phosphorylation. The gene, which is present on chromosome 5, has a product longer than any other reported for a P-type ATPase. Interstrain analysis from 12 parasite isolates by the polymerase chain reaction reveals that a 330-bp nucleotide sequence encoding three cytoplasmic regions conserved in cation ATPases (regions a-c) is of constant length. By contrast, another 360-bp sequence which is one of four regions we refer to as

Sequence homology between RNAs encoding rat α-fetoprotein and rat serum albumin

We have determined the sequences of the recombinant DNA inserts of three bacterial plasmid cDNA clones containing most of the rat α-fetoprotein mRNA. The resultant nucleotide sequence of α-fetoprotein was exhaustively compared to the nucleotide sequence of the mRNA encoding rat serum albumin. These two mRNAs have extensive homology (50%) throughout and the same intron locations. The amino acid sequence of rat α-fetoprotein has been deduced from the nucleotide sequence, and its comparison to rat serum albumin's amino acid sequence reveals a 34% homology. The regularly spaced positions of the cysteines found in serum albumin are conserved in rat α-fetoprotein, indicating that these two proteins may have a similar secondary folding structure. These homologies indicate that α-fetoprotein and serum albumin were derived by duplication of a common ancestral gene and constitute a gene family

Identification and Analysis of Novel Amino-Acid Sequence Repeats in Bacillus anthracis str. Ames Proteome Using Computational Tools

We have identified four repeats and ten domains that are novel in proteins encoded by the Bacillus anthracis str. Ames proteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2) 122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4) 109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6) 84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8) 36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75-amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53-amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure