Many human pathogens need to extract lipids from their environment for survival and proliferation. How the lipid uptake is accomplished on a molecular level is largely unknown, and no proteins directly involved in this process have been characterized to date. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213) from Mycoplasma pneumoniae, a human pathogen responsible for approximately 30% of community-acquired human pneumonia. Fluorescence microscopy, using antibodies raised against the ectodomain of P116, shows a ubiquitous distribution of P116 on the cell surface, indicating a direct role in host cell interactions. Single-particle cryo-electron microscopy at 3.3 Å resolution reveals two homodimers connected by a dimerization interface, and a core domain presenting a previously unseen fold. This fold creates a large cavity of ~18,000 Å3 with a fully hydrophobic internal surface that is accessible to solvent. The hydrophobic residues lining the cavity are conserved in P116 orthologues of other Mycoplasma species. We also observed elongated densities with a length of 10-19 Å long and a width of 4 Å within the cavity, which are not accounted for by the structure and which we identified as the essential lipids phosphatidylcholine, sphingomyelin and cholesterol using mass spectrometry. When the cavity is emptied by stringent treatment with detergents, the protein undergoes an extensive conformational change to adopt a closed conformation that no longer allows for the accommodation of lipids. We conducted radioactivity transfer experiment demonstrating a net transfer of cholesterol from high-density lipoproteins (HDLs) to P116, and observed an uptake of cholesterol into previously-emptied P116 from serum. We also found a direct attachment of P116 to HDLs using cryo-electron microscopy. These results reveal the mechanism by which P116 captures essential lipids from the host environment and possibly then delivers them by a wringing movement into the membrane by passive transport.