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NIH CryoEM Webinars 2023

Breaking the iron piracy code in pathogenic Neisseria

Ms. Shubham Dubey & Ms. Michelle Bush, Purdue University


Neisseria gonorrhoeae (Ngo) and Neisseria meningitidis (Nme) are obligate human pathogens that cause gonorrhea and meningitis, respectively. Although vaccines are available for Nme, they are not universally effective; there are no vaccines against Ngo. To make matters worse, the rapid emergence of drug-resistant Ngo has led to its threat level to public health being elevated to ‘urgent’ by the CDC. Therefore, there is an immediate need for novel antibiotics and vaccine discovery to combat these pathogens.

Recent efforts towards novel therapeutics against Neisseria have focused on surface-exposed membrane protein machineries that are essential for pathogenesis, such as the transferrin-binding protein (Tbp) system. The Tbp system consists of a surface TonB-dependent transporter called TbpA and a lipoprotein co-receptor called TbpB. Together, these proteins orchestrate the extraction of iron from human transferrin (TF). While structures of TbpA and TbpB have been reported, the mechanism for iron piracy remains elusive.

To better understand Tbp-mediated iron acquisition from TF, we determined multiple cryo-EM structures of the Tbp system in complex with TF at distinct stages along the iron acquisition pathway. These structural studies have revealed novel mechanistic insights that have shifted the current paradigm for this system. Overall, our results provide essential details necessary for deciphering the mechanism that Neisseria use to mediate iron piracy during pathogenesis.

About Ms. Shubham Dubey & Ms. Michelle Bush

Graduate Students Department of Biological Sciences

Audience: Public