Asset Details
Do you wish to reserve the book?
Crystal structure of the ICMR-ICMG complex: Implications for a type IVB secretion system in Legionella pneumophila
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Crystal structure of the ICMR-ICMG complex: Implications for a type IVB secretion system in Legionella pneumophila
Do you wish to request the book?
Crystal structure of the ICMR-ICMG complex: Implications for a type IVB secretion system in Legionella pneumophila
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Dissertation
Crystal structure of the ICMR-ICMG complex: Implications for a type IVB secretion system in Legionella pneumophila
2010
Overview
Legionella pneumophila (Lp) is a gram-negative pathogen that is the causative agent of Legionnaire's disease. Once endocytosed by alveolar macrophages, Lp subverts the endosome-lysosome pathway and converts the endosome into an ER-like compartment where the bacterium replicates. Conversion of the endosome into an ER-like compartment requires ∼26 Dot/Icm genes that encode a Type IVb secretion system (T4bSS). The T4bSS is evolutionarily-related to the Incl plasmid conjugation system and also has 7 novel genes. IcmR and icmQ are novel genes and mutation studies revealed that they are essential for intracellular replication. IcmQ is composed of two domains: an N-terminal domain (Qn) and a C-terminal domain (Qc). The Qn domain interacts with the middle region of IcmR (Rm). A previous structure of Rm-Qn interacting domains revealed a four helix bundle (4HB), in which two helices each are contributed respectively by IcmR and IcmQ. In this thesis, crystals of the Rm-IcmQ complex were obtained and the structure was solved by single-wavelength anomalous dispersion (SAD) phasing with selenomethionine labeled complexes. Remarkably, the Qc domain in the IcmR-IcmQ complex has a fold similar to NAD-binding domains in bacterial toxins, such as cholera, diphtheria and pertussis toxins. Each of these toxins exhibits ADP-ribosyltransferase activity; hence, the structure of Qc suggests that it may also have this activity. In support of this idea, binding studies indicated that the Qc domain interacts with NAD. In addition, highly conserved residues in the Qc domain that may play a role in NAD binding were identified by comparative modeling. This included residues that may interact with nicotinamide, adenine and phosphate groups of NAD. Importantly, aspartate 151 is predicted to play a critical role in destabilizing the Nglycosidic bond between the nicotinamide and ribose rings. Further studies are now needed to characterize NAD binding and to identify the substrate of the IcmR-IcmQ complex. This substrate is predicted to function in the T4bSS and ADP-ribosylation by the Qc domain may promote assembly of the T4bSS or regulate its function. This work points the way to obtain a deeper understanding of IcmR-IcmQ function in the T4bSS and suggests a drug target for treating Legionella infections.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
1124296093, 9781124296098
