Montana State University

College of Letters & Science

Montana State University
P.O. Box 172360
Bozeman, MT 59717-2360

Tel: (406) 994-4288
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E-mail: lands@montana.edu
Location: 2-205 Wilson Hall

P. Lynne Howell, University of Toronto
November 18, 2011

   
 
 

Speaker: P. Lynn Howell

Canada Research Chair in Structural Biology

Senior Scientist and Program Head, Program in Molecular Structure and Function, The Hospital for Sick Children

Professor, Department of Biochemistry, University of Toronto

Date: Friday, November 18, 2011
Place: Byker Auditorium (Chemistry & Biochemistry Building)
Time: 3:10 PM

Title: Structural Insight Into Alginate Biosynthesis and Export

Sponsoring department: Microbiology

Summary
: Pseudomonas aeruginosa causes chronic biofilm infections in the lungs of cystic fibrosis patients, which are characterized by the overproduction of the exopolysaccharide alginate. Alginate is synthesized from GDP-mannuronate, post-translationally modified in the periplasm, and exported from the cell by ten proteins encoded by the algD operon. We have begun to map out the protein-protein interactions that exist in the alginate biosynthetic complex using a variety of techniques, and have found that a subcomplex of the periplasmic proteins AlgG, AlgL, AlgX, and the outer membrane lipoprotein, AlgK exists.  The presence of AlgK in this subcomplex is consistent with its structure, which we have shown contains multiple copies of the TPR protein-protein interaction motif and its potential role in aligning the biosynthetic machinery in the inner membrane and periplasm with the outer membrane export protein, AlgE. Our recent structure determination of AlgE reveals that this protein is a monomeric 18-stranded β-barrel with a highly electropositive pore constriction formed by an arginine-rich conduit, which is occluded on either side by extracellular loop L2 and an unusually long periplasmic loop, T8. Halide efflux assays show that deletion of loop T8 (DT8-AlgE) results in a three-fold increase in ion flux compared to the wild-type or DL2-AlgE proteins, suggesting T8 may play a role in regulating alginate secretion. Our model regarding how AlgE functions at the molecular level to allow alginate export as well as our findings on the other members of the periplasmic complex will be presented.

About the speaker: Dr. P. Lynne Howell is a Senior Scientist in the Program in Molecular Structure and Function at The Hospital for Sick Children and a Professor in the Department of Biochemistry, University of Toronto.  Dr. Howell is interested in the development of novel antibiotics and is currently focused on metabolic enzymes that regulate and phenomena that are critical for bacterial biofilm development. Using a combination of structural biology, biochemistry and microbiology, Dr. Howell’s research seeks to understand at the molecular level: the structure and function of enzymes in the methionine recycling pathway; how the virulence factor type IV pili (T4P), used by P. aeruginosa to establish infections and for biofilm formation, is assembled; and how the exopolysaccharide alginate, the major component of bacterial biofilms in cystic fibrosis patients, is synthesized, post-translationally modified, and exported from the cell. Dr. Howell holds a Canada Research Chair in Structural Biology and is currently Head of the Program in Molecular Structure and Function at The Hospital for Sick Children.

Dr. Howell obtained an undergraduate degree in Biophysics from the University of Leeds in 1983.  She received her Ph.D. from the University of London in 1986 in the laboratory of Professor Julia Goodfellow.  Dr. Howell spent three years as a postdoctoral fellow under the mentorship of Professor Gregory A. Petsko at Massachusetts Institute of Technology before moving to Paris for two years to study with Dr. Roberto Poljak and Dr. Andre Menez at the Institute Pasteur. She joined The Hospital for Sick Children in late 1991 and was cross-appointed to the University of Toronto shortly afterwards.  Dr. Howell is a former recipient of a Canadian Institutes of Health Research Investigator Award.

Poster