Naima Sharaf got her undergraduate degree in Chemistry at the University of North Carolina-Chapel Hill. She carried out her Ph.D. studies at the University of Pittsburgh in the lab of Dr. Angela Gronenborn where she used fluorine solution NMR to understand inhibitor-induced conformational changes with HIV-1 reverse transcriptase. To expand her structural biology skill set, she undertook postdoctoral training at Caltech in the lab of Dr. Doug Rees where she characterized the structure and function of the Neisseria meningitides methionine ABC transport system using x-ray crystallography and single-particle cryo-EM. This research sparked Dr. Sharaf's current interest in lipoproteins, particularly their roles in bacterial physiology and potential in vaccine design. Research in the Sharaf Lab bridges biochemistry, biology, microbiology, and immunology to translate lipoprotein research into therapeutics.
Current Research and Scholarly Interests
Proteins embedded in the cell envelope of bacteria perform multiple important functions, including signaling, nutrient acquisition, and export of virulence factors. Understanding the structure and functions of these proteins is critical for the development of new anti-bacterial therapies. Currently, the lab focuses on both ABC transporters and lipoproteins of Gram-negative bacteria. The ultimate goal of our research is to translate basic lipoprotein research into novel therapeutics.
Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that lipidated MetQ is required for interaction
NmMetQ is a substrate-binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To elucidate the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the presence and absence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function and localization, playing a role in NmMetNI-mediated transport at the inner membrane and moonlighting on the bacterial surface.
View details for DOI 10.7554/eLife.69742
View details for Web of Science ID 000693095000001
View details for PubMedID 34409939
View details for PubMedCentralID PMC8416018