טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentChulsky Elena
SubjectTransport of Trace Metals in Bacteria
DepartmentDepartment of Medicine
Supervisor Professor Oded Lewinson
Full Thesis textFull thesis text - English Version


Abstract

Transport across membranes is one of the basic functions in any living organism; most of the molecules enter or leave the cells aided by proteins. One of the largest transport system superfamily is the ATP Binding Cassette transporter (ABC transporters). Transporters that belong to this family share a common domain organization and these structural similarities led to suggestion of a conserved mechanism of substrate transport. We studied two ABC import systems with the same substrate specificity. Our findings showed that there is significant mechanistic divergence among ABC transporters, even when they share the same substrate specificity. We propose that these differences are correlated with the different folds of the transmembrane domains of ABC transporter.

ABC transporters of trace metals are involved in bacterial pathogenicity. Here we studied the metal binding spectrum of a putative metal import system, MntBCA which was recently identified as a major virulence determinant of the lethal bacterium, Bacillus anthracis. We determined the metal binding specificity of the system's substrate binding protein, MntA, and identified the residues that participate in meal coordination. Moreover, our in-vivo experiments are in agreement with the in-vitro biochemical characterization of MntA, proposing that MntBCA is a manganese import system.

In addition, we present preliminary biochemical and structural data of YobA, the metal binding component of a putative copper importer of E. coli.