Perez Lab
Mechanisms of Cell Wall Assembly

Mechanistic basis of teichoic acid transport by a gatekeeper flippase Link to publication in Nat .Commun. The cell wall is a complex structure that protects bacteria from environmental threats. Phosphocholine-containing teichoic acids are key cell wall biopolymers for the human pathogen Streptococcus pneumoniae. The flippase TacF, a member of the multidrug/oligosaccharide-lipid/polysaccharide (MOP) superfamily, monitors the phosphocholine content of teichoic acids during transport, yet the underlying mechanism of this process remains unknown. In our work, we present a cryo-EM structure of S. pneumoniae TacF in lipid nanodiscs, which, through complementary multidisciplinary approaches, provides mechanistic insights into TacF's molecular mechanism. In addition, our studies reveal common mechanistic elements among MOP flippases, indicating a shared mechanism for polyprenyl-diphosphate-linked oligosaccharide lipid transport. 

Receptor-recognition and antiviral mechanisms of retrovirus-derived human proteins. Link to publication in NSMB In collaboration with the Reyes Lab we present cryo-electron microscopy structures and functional characterization of human ASCT2 in complexes with the receptor-binding domains of syncytin-1 and suppressyn, cellular proteins of retroviral origin involved in cell–cell fusion events to establish the maternal–fetal interface in the placenta. Our work uncovers a common ASCT2 recognition mechanism by a large group of endogenous and disease-causing retroviruses, and provides high-resolution views on how placental human proteins exert morphological and immunological functions.

Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification 
Link to publication in Sci. Adv.

We determined the structure and mechanism of LicB, a choline transporter involved in the cell wall biosynthesis of Streptococcus pneumoniae. We used a multidisciplinary approach including structure determination by cryo-EM and X-ray crystallography, electrophysiology, in-vitro transport assays, sybody generation in collaboration with the Seeger Lab, and in- vivo assays in collaboration with the Veening Lab.

Evidence for a trap-and-flip mechanism in a proton-dependent lipid transporter
Link to publication in Nat. Commun.

We investigated the flipping mechanism of LtaA, a proton-dependent MFS lipid transporter essential for lipoteichoic acid biosynthesis in the pathogen Staphylococcus aureus. Combining cysteine disulfide trapping, mutagenesis, transport assays in vitro and in vivo, and molecular dynamics simulations in collaboration with the Mehdipour Lab and Hummer Lab, we revealed that LtaA catalyzes lipid translocation by a trap-and-flip mechanism.