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T M Yi

Publications and source records attributed to T M Yi.

7 recordsLinked to original sources
PubMed2000

Robust perfect adaptation in bacterial chemotaxis through integral feedback control.

Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In biological systems, it is common for the response to an extracellular stimulus to return to its prestimulus value even in the continued presence of the signal-a process termed adaptation or desensitization. Barkai, Alon, Surette, and Leibler have provided both theoretical and experimental evidence that the precision of adaptation in bacterial chemotaxis is robust to dramatic changes in the levels and kinetic rate constants of the constituent proteins in this signaling network [Alon, U., Surette, M. G., Barkai, N. & Leibler, S. (1998) Nature (London) 397, 168-171]. Here we propose that the robustness of perfect adaptation is the result of this system possessing the property of integral feedback control. Using techniques from control and dynamical systems theory, we demonstrate that integral control is structurally inherent in the Barkai-Leibler model and identify and characterize the key assumptions of the model. Most importantly, we argue that integral control in some form is necessary for a robust implementation of perfect adaptation. More generally, integral control may underlie the robustness of many homeostatic mechanisms.

Acclimatization↗
PubMed1994

Recognition of related proteins by iterative template refinement (ITR).

Predicting the structural fold of a protein is an important and challenging problem. Available computer programs for determining whether a protein sequence is compatible with a known 3-dimensional structure fall into 2 categories: (1) structure-based methods, in which structural features such as local conformation and solvent accessibility are encoded in a template, and (2) sequence-based methods, in which aligned sequences of a set of related proteins are encoded in a template. In both cases, the programs use a static template based on a predetermined set of proteins. Here, we describe a computer-based method, called iterative template refinement (ITR), that uses templates combining structure-based and sequence-based information and employs an iterative search procedure to detect related proteins and sequentially add them to the templates. Starting from a single protein of known structure, ITR performs sequential cycles of database search to construct an expanding tree of templates with the aim of identifying subtle relationships among proteins. Evaluating the performance of ITR on 6 proteins, we found that the method automatically identified a variety of subtle structural similarities to other proteins. For example, the method identified structural similarity between arabinose-binding protein and phosphofructokinase, a relationship that has not been widely recognized.

Amino Acid Sequence↗
PubMed1993

Protein secondary structure prediction using nearest-neighbor methods.

We have studied the use of nearest-neighbor classifiers to predict the secondary structure of proteins. The nearest-neighbor rule states that a test instance is classified according to the classifications of "nearby" training examples from a database of known structures. In the context of secondary structure prediction, the test instances are windows of n consecutive residues, and the label is the secondary structure type (alpha-helix, beta-strand, or coil) of the center position of the window. To define the neighborhood of a test instance, we employed a novel similarity metric based on the local structural environment scoring scheme of Bowie et al. In this manner, we have attempted to exploit the underlying structural similarity between segments of different proteins to aid in the prediction of secondary structure. Furthermore, in addition to using neighborhoods of fixed radius, we explored a modification of the standard nearest-neighbor algorithm that involved defining an "effective radius" for each exemplar by measuring its performance on a training set. Using these ideas, we achieved a peak prediction accuracy of 68%. Finally, we sought to improve the biological utility of secondary structure prediction by identifying the subset of the predictions that are most likely to be correct. Toward this end, we developed a nearest-neighbor estimator that produced not the traditional "one-state" prediction (alpha-helix, beta-strand, or coil) but rather a probability distribution over the three states. It should be emphasized that this scheme estimates true probability values and that the resulting numbers are not pseudo-probability scores generated by simple normalization of the raw output of the predictor. Applying the mutual information statistic, we found that these probability triplets possess 58% more information than the one-state predictions. Furthermore, the probability estimates allow one to assign an a priori confidence level to the prediction at each residue. Using this approach, we found that the top 28% of the predictions were 86% accurate and the top 43% of the predictions were 81% accurate. These results indicate that, notwithstanding the limitations on overall accuracy of secondary structure prediction, a substantial proportion of a protein can be predicted with considerable accuracy.

Algorithms↗
PubMed1991

Rabbit muscle creatine kinase: genomic cloning, sequencing, and analysis of upstream sequences important for expression in myocytes.

Muscle creatine kinase (MCK) is a major enzyme of cellular energy metabolism that is expressed upon differentiation of myoblasts into myotubes. Previously we cloned and sequenced the entire rabbit enzyme cDNA which was used as a probe in these studies to obtain a genomic clone from a rabbit library. The transcription start site was identified by primer extension analysis and over 800 bp of 5' flanking DNA was sequenced. Comparison of this sequence with the published sequences from the upstream regions of the mouse MCK gene and the human MCK gene showed two conserved regions and a large intervening block of non-conserved sequence. The conserved regions are separated by about 800 bp in the mouse and by about 400 bp in the human, but are much closer (200 bp) in the rabbit. The upstream conserved region of the mouse gene encompasses a region possessing the properties of an enhancer and containing two MyoD binding sites; the downstream element is adjacent to the start of transcription. A set of of overlapping deletions of the 5' upstream DNA was fused to the CAT gene and transfected into mouse C2 myocytes, chick primary myocytes, and chick primary liver cells. Constructs which contained both conserved 5' regions were strongly expressed in C2 and chick myocytes, but were not expressed (above background) in primary liver cells. Surprisingly, while the upstream enhancer element was required for strong expression in C2 myocytes, it was less important for expression in chick myocytes. This suggests that there are important muscle-specific transcriptional signals in the proximal promoter region of mammalian MCK genes.

Animals↗
PubMed1991

Identification of single-stranded-DNA-binding proteins that interact with muscle gene elements.

A sequence-specific DNA-binding protein from skeletal-muscle extracts that binds to probes of three muscle gene DNA elements is identified. This protein, referred to as muscle factor 3, forms the predominant nucleoprotein complex with the MCAT gene sequence motif in an electrophoretic mobility shift assay. This protein also binds to the skeletal actin muscle regulatory element, which contains the conserved CArG motif, and to a creatine kinase enhancer probe, which contains the E-box motif, a MyoD-binding site. Muscle factor 3 has a potent sequence-specific, single-stranded-DNA-binding activity. The specificity of this interaction was demonstrated by sequence-specific competition and by mutations that diminished or eliminated detectable complex formation. MyoD, a myogenic determination factor that is distinct from muscle factor 3, also bound to single-stranded-DNA probes in a sequence-specific manner, but other transcription factors did not. Multiple copies of the MCAT motif activated the expression of a heterologous promoter, and a mutation that eliminated expression was correlated with diminished factor binding. Muscle factor 3 and MyoD may be members of a class of DNA-binding proteins that modulate gene expression by their abilities to recognize DNA with unusual secondary structure in addition to specific sequence.

Animals↗
PubMed1988

Illegitimate recombination in an Escherichia coli plasmid: modulation by DNA damage and a new bacterial gene.

We studied DNA rearrangements in Escherichia coli by using a plasmid-based system with a transcriptionally silent tet gene and selecting for Tetr isolates. The predominant activating event was a 1.3-kilobase-pair deletion in the plasmid between two sites, with 14 of 19 base pairs being identical. These deletions occurred equally frequently in a recA+ strain and a recA13 mutant. However, the frequency of Tetr occurrence was stimulated 50-fold by treatment of the cells with UV light in a process that was at least partly independent of the SOS response. Bacterial mutants deleted for the xth-pnc region of the chromosome exhibited a strongly elevated spontaneous frequency of Tetr isolates, all with the same 1.3-kilobase-pair deletion. This phenotype of high-frequency deletion could be complemented by an episome covering this region, but not by the cloned xth gene. These studies helped to define the role of different DNA damages in illegitimate recombination and identify a region of the E. coli chromosome that contains a gene whose product normally suppresses illegitimate deletions.

Base Sequence↗