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Proteins as Chameleons: The Good, the Bad and the Ugly

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Air date: Wednesday, April 14, 2010, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 96 * This only includes stats from October 2011 and forward.
Category: WALS - Wednesday Afternoon Lectures
Runtime: 01:08:04
Description: Proteins are not merely the products from gene translation, but may undergo extensive co- and post-translational modifications that result in significant divergence from the plan of the template. And some are not even template-driven! Full understanding of normal and aberrant protein structure/function relationships requires not only identification and quantification of proteins that indicate which cellular pathways are affected under the conditions chosen for study, but also characterization of post-translational modifications (PTMs) to these proteins [1]. Antibody-based pull-down methods retrieve molecular complexes whose composition can vary depending on the presence of sequence elements or PTMs of key proteins [2]. Alternatively, chemical modifications to specific amino acids (e.g., ICAT, fluorolabels) or isolation methods that are based on chemical interactions (e.g., with phosphate groups) enable the enrichment of proteins/peptides that bear specific markers for processes such as oxidative stress, protein misfolding, or cancer [1-6]. We have developed strategies for separation of intact proteins or peptides and for determination of their complete amino acid sequences and the identification and site-specific localization of PTMs. If the PTMs are labile under routine MS conditions (e.g., phosphorylation, sulfonation, glycosylation), particular attention needs to be paid to the selection of dissociation conditions that preserve and, ultimately, fully define the modification(s). When individual proteins have multiple PTMs, only analysis of the intact proteins will provide information on the correlations between PTMs. Isolated proteins may be subjected to proteolytic or chemical degradation (bottom-up ↑) or analyzed in their intact form (top-down ↓). Examples from recent and ongoing projects will be presented to illustrate some of the proteomic and glycomic strategies developed and utilized in our Center to catch the elusive chameleons.

The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.
NLM Title: Proteins as chameleons : the good, the bad, and the ugly / Catherine Costello.
Author: Costello, Catherine E.
National Institutes of Health (U.S.)
Publisher:
Abstract: (CIT): Proteins are not merely the products from gene translation, but may undergo extensive co- and post-translational modifications that result in significant divergence from the plan of the template. And some are not even template-driven! Full understanding of normal and aberrant protein structure/function relationships requires not only identification and quantification of proteins that indicate which cellular pathways are affected under the conditions chosen for study, but also characterization of post-translational modifications (PTMs) to these proteins [1]. Antibody-based pull-down methods retrieve molecular complexes whose composition can vary depending on the presence of sequence elements or PTMs of key proteins [2]. Alternatively, chemical modifications to specific amino acids (e.g., ICAT, fluorolabels) or isolation methods that are based on chemical interactions (e.g., with phosphate groups) enable the enrichment of proteins/peptides that bear specific markers for processes such as oxidative stress, protein misfolding, or cancer [1-6]. We have developed strategies for separation of intact proteins or peptides and for determination of their complete amino acid sequences and the identification and site-specific localization of PTMs. If the PTMs are labile under routine MS conditions (e.g., phosphorylation, sulfonation, glycosylation), particular attention needs to be paid to the selection of dissociation conditions that preserve and, ultimately, fully define the modification(s). When individual proteins have multiple PTMs, only analysis of the intact proteins will provide information on the correlations between PTMs. Isolated proteins may be subjected to proteolytic or chemical degradation (bottom-up) or analyzed in their intact form (top-down). Examples from recent and ongoing projects will be presented to illustrate some of the proteomic and glycomic strategies developed and utilized in our Center to catch the elusive chameleons.
Subjects: Protein Processing, Post-Translational.
Proteins--metabolism
Publication Types: Lecture
Webcast
NLM Classification: QU 475
NLM ID: 101531587
CIT Live ID: 8694
Permanent link: https://videocast.nih.gov/watch=8694