Many ATP-binding cassette (ABC) transporters are regulated by phosphorylation on long and disordered loops which present a challenge to visualize with structural methods. We have trapped an activated state of the regulatory domain (R-domain) of Yeast Cadmium Factor 1 (Ycf1) by enzymatically enriching the phosphorylated state. A 3.2 Å cryo-EM structure reveals an R-domain structure with four phosphorylated residues and a position for the entire R-domain. The structure reveals key R-domain interactions including a bridging interaction between NBD1 and NBD2 as well as an interaction with the R-insertion, another regulatory region. We systematically probe these interactions with a linker substitution strategy along the R-domain and find a close match with these interactions and survival under Ycf1-dependent growth conditions. We propose a model where four overlapping phosphorylation sites bridge several regions of Ycf1 to engage in a transport-competent state.
PH-20 is a specific type of hyaluronidase that plays a critical role in the fertilization process by facilitating the initial binding of sperm to the glycoprotein layer surrounding the oocyte and subsequently breaking down hyaluronic acid polymers in the cumulus cell layer. PH-20 contains an epidermal growth factor (EGF)-like domain, which may be involved in the recognition of the glycoprotein layer in addition to the catalytic domain. Herein, we report the structure of human PH-20 determined by cryogenic electron microscopy.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China; Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:
ATP-binding cassette (ABC) transporter subfamily H is only identified in arthropods and zebrafish. It transports lipids and is related to insecticide resistance. However, the precise mechanisms of its functions remain elusive.
Pannexin-3 (PANX3) is a member of the pannexin family of large-pore, ATP-permeable channels conserved across vertebrates. PANX3 contributes to various developmental and pathophysiological processes by permeating ATP and Ca ions; however, the structural basis of PANX3 channel function remains unclear. Here, we present the cryo-EM structure of human PANX3 at 2.
The solute carrier family 15 members 3 and 4 (SLC15A3 and SLC15A4) are closely related endolysosomal peptide transporters that transport free histidine and certain dipeptides from the lumen to cytosol. Besides, SLC15A4 also functions as a scaffold protein for the recruitment of the adapter TASL for interferon regulatory factor 5 (IRF5) activation downstream of innate immune TLR7-9 signaling. However, the molecular basis for the substrate recognition and TASL recruitment by these membrane proteins is not well understood.
Study of mechanisms by which antibodies recognize different viral strains is necessary for the development of new drugs and vaccines to treat COVID-19 and other infections. Here, we report 2.5 Å cryo-EM structure of the SARS-CoV-2 Delta trimeric S-protein in complex with Fab of the recombinant analog of REGN10987 neutralizing antibody.
