Hofmann1, Januliene1, Mehdipour1, Thomas, Stefan, Bruechert, Kuhn, Geertsma, Hummer, Tampe* & Moeller*

The conformation space of a heterodimeric ABC transporter under turnover conditions. NATURE 2019

ABC transporters are involved in multi-drug resistance in bacteria and cancer and are significant targets for therapeutics. They promiscuously move cargo across the lipid bilayer, utilizing ATP, which triggers large conformational changes. Using cryo-EM under turnover conditions, we have mapped the conformational space of a single heterodimeric ABC transporter and have identified a previously unknown state, which provides the missing link within the translocation cycle. Furthermore, we have characterized the mechanism of substrate binding and identified the origin of the two power strokes that drive the conformational changes. We are aiming to address the underlying molecular details in subsequent studies.  DOI: 10.1038/s41586-019-1391-0

Timcenko1, Lyons1, Januliene1, Ulstrup, Dieudonne, Montigny, Ash, Karlsen, Boesen, Kühlbrandt, Lenoir*, Moeller* & Nissen*

Structure and autoregulation of a P4-ATPase lipid flippase NATURE 2019

Many biological processes, like membrane dynamics, signaling, endocytosis, and exocytosis, depend on the asymmetric lipid composition between the two membrane leaflets. Lipid flippases (P4-ATPases) and floppases (typically, ABC transporters) are membrane proteins that actively distribute lipids. Using cryo-
EM, we have solved the structure of yeast lipid flippase in three different states, which provide a molecular perspective into the mechanism of auto-regulation in the P-type ATPases. DOI: 10.1038/s41586-019-1344-7

Blees1, Januliene1, Hofmann, Koller, Schmidt, Trowitzsch*, Moeller* & Tampe*

Structure of the human MHC-I peptide-loading complex. NATURE 2017

In adaptive immunity, the antigen-specific immune response relies on the detection and elimination of infected cells through cytotoxic T-cells. The infected cells present the pathogenic peptides on their surface via the MHC-I molecules, which are charged in the peptide-loading complex (PLC). The PLC is a transient,
multisubunit membrane complex, located in the endoplasmic reticulum. We used cryo-EM to decipher the general architecture of this highly flexible complex and solved multiple structures of PLC, captured at distinct assembly states, which provide important mechanistic insights into the MHC-I recruitment and release. DOI: 10.1038/nature24627