Multiple-alphabet amino acid sequence comparisons of the immunoglobulin kappa-chain constant domain.

Karlin, Samuel; Ghandour, Ghassan

doi:10.1073/pnas.82.24.8597

Cited by 37 publications

(12 citation statements)

References 17 publications

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“…Therefore, we aligned and compared the amino acid sequences of these two proteins and noted that there were 28 differences. When these amino acids are grouped according to their chemical composition (41), 17 of the 28 differences are not conserved (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

Interaction of Zyxin, a Focal Adhesion Protein, with the E6 Protein from Human Papillomavirus Type 6 Results in Its Nuclear Translocation

Degenhardt¹,

Silverstein

2001

J Virol

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Zyxin, a focal adhesion molecule, interacts specifically with the E6 protein from human papillomavirus (HPV) type 6 in a yeast two-hybrid screen of a cDNA library prepared from human keratinocytes. Zyxin does not interact significantly with E6 proteins from HPV types 11, 16, or 18. The interaction was confirmed by in vitro and in vivo analyses and it requires the LIM domains (Lin-11, Isl-1, and Mec-3 [G. Freyd, S. K. Kim, and H. R. Horvitz, Nature 344:876-879, 1990]) found at the carboxyl terminus of zyxin. Cotransfection of E6 from HPV ( 6 E6) and zyxin results in the accumulation of zyxin in the nucleus where it can function as a transcriptional activator. 6 E6 can also mobilize endogenous zyxin to the nucleus.Human papillomaviruses (HPVs) are responsible for hyperproliferation of cutaneous and mucocutaneous epithelial cells that can lead to propagation of benign (30) or malignant (81) lesions depending on the virus type. The E6 and E7 proteins encoded by mucocutaneous high-risk types interact with p53 (65, 77) and the retinoblastoma (Rb) protein family (50), respectively, and transform cells in culture (10,35,39,49,74). In contrast, the E6 and E7 proteins encoded by low-risk viruses do not interact with these proteins and are not typically associated with events that lead to cell transformation (6).The E6 proteins encoded by HPVs contain about 150 amino acids and possess two Cys-X-X-Cys zinc fingers that bind zinc (5). While host proteins that interact with the E6 protein from both low-and high-risk HPVs (22,44,45,54,69) or only from high-risk HPVs have been identified (16, 26-28, 40, 42, 47, 57, 60, 70), no specific interaction between low-risk E6 and host proteins has been described. Here we report that low-risk E6 from HPV type 6 ( 6 E6) interacts with zyxin, a focal adhesion protein (7).Focal adhesion plaques are discrete areas on the cell membrane where the cells contact the underlying substratum or each other (36, 75). They are also the sites where multiple protein complexes involved in signaling assemble (15). Focal adhesions appear to represent transmembrane connections between the extracellular matrix and the cytoskeleton. Thus, it is not surprising that disrupted focal adhesions are frequently associated with the transformed phenotype (14). The E6 proteins from bovine papillomavirus and high-risk HPV interact with paxillin, another focal adhesion protein (13,70,71). This interaction may in part account for the disruption of actin fiber organization when bovine papillomavirus type 1 E6 is overexpressed in cells (70).Zyxin has features reminiscent of a signaling protein. Relative to the structural components of focal adhesions such as vinculin and ␣-actinin it is present at low abundance in cells and it is phosphorylated at multiple sites in vivo (18). Structurally, it has a proline-rich domain at its N terminus and multiple LIM ) domains in its carboxy-terminal half (8). Both domains are thought to be involved in protein binding (59,66). The proline-rich domain associates with SH3 domains that are f...

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Section: Resultsmentioning

confidence: 99%

Interaction of Zyxin, a Focal Adhesion Protein, with the E6 Protein from Human Papillomavirus Type 6 Results in Its Nuclear Translocation

Degenhardt¹,

Silverstein

2001

J Virol

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“…Other models based on observed sequence variability in large alignments of homologous protein sequences, such as the BLOSUM family [5], have proven popular and successful. Karlin and Ghandour [6] and George, Barker, and Hunt [7] proposed methods of weighting differences based on chemical, functional, charge and structural properties of amino acids and computing replacement probabilities based on the similarity of the involved residues. Doolittle's group proposed substitution matrices based on amino acid structural similarities combined with the ease of genetic interchange [8], while Stanfel added information pertaining to biochemical properties to inform the probability of amino acid interchangeability [9].…”

Section: Introductionmentioning

confidence: 99%

HIV-Specific Probabilistic Models of Protein Evolution

et al. 2007

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Comparative sequence analyses, including such fundamental bioinformatics techniques as similarity searching, sequence alignment and phylogenetic inference, have become a mainstay for researchers studying type 1 Human Immunodeficiency Virus (HIV-1) genome structure and evolution. Implicit in comparative analyses is an underlying model of evolution, and the chosen model can significantly affect the results. In general, evolutionary models describe the probabilities of replacing one amino acid character with another over a period of time. Most widely used evolutionary models for protein sequences have been derived from curated alignments of hundreds of proteins, usually based on mammalian genomes. It is unclear to what extent these empirical models are generalizable to a very different organism, such as HIV-1–the most extensively sequenced organism in existence. We developed a maximum likelihood model fitting procedure to a collection of HIV-1 alignments sampled from different viral genes, and inferred two empirical substitution models, suitable for describing between-and within-host evolution. Our procedure pools the information from multiple sequence alignments, and provided software implementation can be run efficiently in parallel on a computer cluster. We describe how the inferred substitution models can be used to generate scoring matrices suitable for alignment and similarity searches. Our models had a consistently superior fit relative to the best existing models and to parameter-rich data-driven models when benchmarked on independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid substitution that are unique to HIV, and that are not captured by the existing models. The scoring matrices derived from the models showed a marked difference from common amino-acid scoring matrices. The use of an appropriate evolutionary model recovered a known viral transmission history, whereas a poorly chosen model introduced phylogenetic error. We argue that our model derivation procedure is immediately applicable to other organisms with extensive sequence data available, such as Hepatitis C and Influenza A viruses.

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“…(c) THM1 sequence encompassing the aln mutation is highly conserved across species. In the C. elegans and C. reinhardtii orthologs, the substitution of glutamine by arginine is predicted to be a structurally conservative amino acid substitution 45 . The start methionine is shown for Mus musculus, Bos taurus, Homo sapiens and Gallus gallus orthologs.…”

Section: Supplementary Materialsmentioning

confidence: 99%

THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia

et al. 2008

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Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA-interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in mouse inner medullary collecting duct cells Reprints and permissions information is available online at

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Multiple-alphabet amino acid sequence comparisons of the immunoglobulin kappa-chain constant domain.

Cited by 37 publications

References 17 publications

Interaction of Zyxin, a Focal Adhesion Protein, with the E6 Protein from Human Papillomavirus Type 6 Results in Its Nuclear Translocation

Interaction of Zyxin, a Focal Adhesion Protein, with the E6 Protein from Human Papillomavirus Type 6 Results in Its Nuclear Translocation

HIV-Specific Probabilistic Models of Protein Evolution

THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia

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