Molecular Biology Commons^™

An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien

Honors Scholar Theses

In recent years, several new clades within the domain Achaea have been discovered. This is due in part to microbiological sampling of novel environments, and the increasing ability to detect and sequence uncultivable organisms through metagenomic analysis. These organisms share certain features, such as small cell size and streamlined genomes. Reduction in genome size can present difficulties to phylogenetic reconstruction programs. Since there is less genetic data to work with, these organisms often have missing genes in concatenated multiple sequence alignments. Evolutionary Biologists have not reached a consensus on the placement of these lineages in the archaeal evolutionary tree. There …

Differential Protein Expression During Tail Regeneration Of Anolis Carolinensis, Victor Hong, Benjamin Thornton

Research in Biology

Some invertebrate and vertebrate species have the ability to regenerate a lost limb. The lizard species are unique in that they can autotomize their tails and regrow them back. In this study, the proteomic change occurring within the regenerating tail of Anolis carolinensis (Green anole) during 72 h period was examined. We ran 2-dimension electrophoresis to separate the proteins and utilized SameSpots software to find 6 different spots that had altered expression of protein. Within those spots, proteins involved in immunity, energetics, and protein folding and degradation were identified. The proteins that were up-regulated were transferrin, nucleotide-binding domain of the …

Ring Domain, David J. Hall

Protein Domains

Ring domain #1CHC. The RING finger is a specialized type of Zn finger consisting of 40–60 residues that binds two atoms of zinc, and is involved in mediating protein—protein interactions. Many zinc fingers bind nucleic acids. The presence of a RING finger domain is a characteristic of RING-class E3 ubiquitin protein ligases capable of transferring ubiquitin from an E2 enzyme to a substrate protein.

Sh2 Domain, David J. Hall

Protein Domains

SH2 domain #1BFJ. Src-homology 2 (SH2) domains are modules of ~100 amino acids that bind to specific phospho tyrosine (pY) containing peptide motifs. Conventional SH2 domains have a conserved pocket that recognizes pY, and a more variable pocket that binds 3-6 residues C-terminal to the pY and confers specificity.

Sh3 Domain, David J. Hall

Protein Domains

SH3 domain #1NEB. Src-homology 3 (SH3) domains bind to Pro-rich peptides that form a left-handed poly-Pro type II helix, with the minimal consensus Pro-X-X-Pro. Each Pro is usually preceeded by an aliphatic residue. Each in the aliphatic-Pro pair binds to a hydrophobic pocket on the SH3 domain.

Ig Domain, David J. Hall

Protein Domains

Ig domain #2CKN. This particular domain is named for the first protein in which it was found, the immunoglobulin. An immunoglobulin is a antibody. Antibodies are generated by our immune system to recognize the specific size, shape and charge of pathogens. This domain is also found on the extracellular portion of many receptors including the interleukin-1 family of receptors.

Beta Barrel, David J. Hall

Protein Domains

Beta barrel (cyan fluorescent protein) #4AR7. This fluorescent protein is a variation of green fluorescent protein from a jellyfish and is the only domain that is a complete protein. The protein is routinely used to visualize a variety of biological processes. The beta barrel domain is a beta sheet wrapped around the fluorescent active site to provide structure.

Helix Turn Helix Domain, David J. Hall

Protein Domains

Helix turn helix domain #3V1A. The helix-turn helix is a DNA-binding domain. The two alpha helices are the reading or recognition helices, which bind in a groove in the DNA and recognize specific gene regulatory sequences in the DNA.

Biochemical, Structural, And Drug Design Studies Of Multi-Drug Resistant Hiv-1 Therapeutic Targets, Tamaria Grace Dewdney

Wayne State University Dissertations

Protein point mutations acquired as a mechanism of survival against therapeutics cause structural changes that effect protein function and inhibitor binding. This work investigates the structural mechanisms that lead to multi-drug resistance to HIV-1 protease and integrase inhibitors.

Proper proteolytic processing of the HIV-1 Gag/Pol polyprotein is required for HIV infection and viral replication. This feature has made HIV-1 protease an attractive target for antiretroviral drug design for the treatment of HIV-1 infected patients, thus the development of drug resistance has arisen as a major therapeutic and drug design challenge. To understand the molecular mechanisms leading to drug resistance we …

Protein Expression Analysis Of Cell Lines Derived From Drug Resistant Tumors, Paloma Valenzuela, Karla Parra, Natzidielly Lerma, Courtney Becerril, Eduardo Ramirez, Irving Miramontes, Howard West, Cynthia Rodriguez, Yang Li, Jianying Zhang, Giulio Francia

COURI Symposium Abstracts, Summer 2012

There are a number of effective treatments for breast cancer, including chemotherapy and targeted strategies such as the use of the Her-2 targeting drugs lapatinib and trastuzumab. However, in a number of cases, tumors that initially respond to therapy eventually develop drug resistance, leading to the relapse of the disease. By studying protein levels in different drug resistant variants, we have observed two mechanisms by which drug resistance may develop. Thus, some Her-2 human breast cancer cells (e.g., MDA-MB-231H2N) treated with the clinically used trastuzumab agent, can escape therapy by shedding, or losing, the target Her-2 protein. Similarly, EMT-6 mouse …

Analysis Of The Effects And Current Treatments Of Laminin Deficiency, Joshua Mark Reynolds

Senior Honors Theses

Laminin (LM) is a network of proteins that functions as a connective framework of most cells in the body. It is composed of multiple different subunits and therefore has many different variations. It is a trimeric protein, meaning that it is composed primarily of ⍺, β, and γ chains. The differentiation of these subunits is what gives the different variants their functions. In addition, although LM is the primary molecule in scope, the network of other connective proteins involved in LM-associated diseases will also be covered in lesser detail because molecules like dystrophin, dystroglycan, collagen, and integrin are vital to …

Mimosa: A System For Minimotif Annotation, Jay Vyas, Ronald J. Nowling, Thomas Meusburger, David P. Sargeant, Krishna Kadaveru, Michael R. Gryk, Vamsi Kundeti, Sanguthevar Rajasekaran, Martin Schiller

Life Sciences Faculty Research

BACKGROUND:

Minimotifs are short peptide sequences within one protein, which are recognized by other proteins or molecules. While there are now several minimotif databases, they are incomplete. There are reports of many minimotifs in the primary literature, which have yet to be annotated, while entirely novel minimotifs continue to be published on a weekly basis. Our recently proposed function and sequence syntax for minimotifs enables us to build a general tool that will facilitate structured annotation and management of minimotif data from the biomedical literature.

RESULTS:

We have built the MimoSA application for minimotif annotation. The application supports management of …

Partitioning Of Minimotifs Based On Function With Improved Prediction Accuracy, Sanguthevar Rajasekaran, Tian Mi, Jerlin Camilus Merlin, Aaron Oommen, Patrick R. Gradie, Martin R. Schiller

Life Sciences Faculty Research

Background

Minimotifs are short contiguous peptide sequences in proteins that are known to have a function in at least one other protein. One of the principal limitations in minimotif prediction is that false positives limit the usefulness of this approach. As a step toward resolving this problem we have built, implemented, and tested a new data-driven algorithm that reduces false-positive predictions.

Methodology/Principal Findings

Certain domains and minimotifs are known to be strongly associated with a known cellular process or molecular function. Therefore, we hypothesized that by restricting minimotif predictions to those where the minimotif containing protein and target protein have …

A Proposed Syntax For Minimotif Semantics, Version 1., Jay Vyas, Ronald J. Nowling, Mark W. Maciejewski, Sanguthevar Rajasekaran, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

BACKGROUND:

One of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of …

Minimotif Miner 2nd Release: A Database And Web System For Motif Search, Sanguthevar Rajasekaran, Sudha Balla, Patrick R. Gradie, Michael R. Gryk, Krishna Kadaveru, Vamsi Kundeti, Mark W. Maciejewski, Tian Mi, Nicholas Rubino, Jay Vyas, Martin R. Schiller

Life Sciences Faculty Research

Minimotif Miner (MnM) consists of a minimotif database and a web-based application that enables prediction of motif-based functions in user-supplied protein queries. We have revised MnM by expanding the database more than 10-fold to approximately 5000 motifs and standardized the motif function definitions. The web-application user interface has been redeveloped with new features including improved navigation, screencast-driven help, support for alias names and expanded SNP analysis. A sample analysis of prion shows how MnM 2 can be used.