Dr. Eric R. Geertsma
Junior Professor
Biocenter N200/1.08
Phone +49-(0)69-798-29255
ax: +49-(0)69-798 29244


Beate Braungart
Administrative assistant
Biocenter N200/1.10
Phone +49-(0)69-798-29238
Fax: +49-(0)69-798 29244



Membrane transport proteins play a pivotal role in controlling the internal milieu of the cell, and thereby have a strong effect on cellular physiology. We study solute carriers, one of the most occurring transporter types in all kingdoms of life, but also one that is relatively understudied. Solute carriers are essential transport proteins in human and pathogens, and consequently often causally associated with diseases.
We combine structural and functional studies to obtain a complete mechanistic understanding of transport by solute carriers and to guide our efforts in modulating (activate or inhibit) their transport activities at will.
In parallel and to support these aims, we develop novel enabling technologies for membrane protein research.

Conformation space of a heterodimeric ABC exporter

Cryo-EM has the capacity to capture molecular machines in action. ABC exporters are highly dynamic membrane proteins that extrude a wide range of substances and thereby contribute to essential cellular processes. To reveal how nucleotide binding, hydrolysis, and release are coupled to the conformational dynamics of these proteins, were determined eight high-resolution cryo-EM structures using a conformationally non-selective nanobody. These structures delineate the full functional cycle of an asymmetric ABC exporter in a lipid environment.
Work from the Moeller and Tampé labs in collaboration with the Hummer and Geertsma labs.
Hofmann, Januliene, and Mehdipour et al., 2019

Structural basis for functional interactions in SLC26 dimers

The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. While the only experimental SLC26 structure is monomeric, SLC26 proteins form structural and functional dimers in the lipid membrane. Here we resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize its functional relevance by combining DEER distance measurements and biochemical studies with MD simulations and spin-label ensemble refinement. Our structural model reveals a unique interface and highlights its functional relevance.
In collaboration with the Hummer and Joseph laboratories.
Chang, Jaumann, and Reichel et al., 2019

Synthetic single domain antibodies for trapping membrane proteins

Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections on challenging targets such as membrane proteins or protein complexes and selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies.
Work from the Seeger, Dawson, and Geertsma laboratories.
Zimmermann et al., 2018

Fumarate transporter structure defines architecture of the SLC26 family.

Membrane proteins of the SLC26 family can be found all over the human body. Most function as secondary anion transporters, except for SLC26A5 or Prestin which is a motor protein responsible for the amplification of sound in the cochlea. We have determined the structure of SLC26Dg, a prokaryotic SLC26 homologue. Its modular structure combines a transmembrane unit of two intertwined repeats of seven transmembrane segments and a cytoplasmic STAS domain. This fold strengthens a common descent of SLC26 and vitamin C transporters.
Work from the Geertsma and Dutzler labs in collaboration with the Steyaert laboratory.
Geertsma et al., 2015

Bicistronic mRNAs to enhance membrane protein overexpression.

A common strategy to improve membrane protein overexpression is the use of fusion proteins, such as MBP and thioredoxin. Here we explore whether similar positive effects can be established using only the mRNA sequence of the fusion protein. In contrast to translational fusions, such transcriptional fusions do not require protease treatment and subsequent removal of the fusion protein. Using this strategy we observed improvements in the quantity and/or the quality for several membrane proteins to levels compatible with structural studies.
In collaboration with the Seeger and Zerbe laboratories.
Marino et al., 2015

SLC11 structure reveals the basis for transition-metal ion transport.

Members of the SLC11 (or NRAMP) family transport iron and other transition-metal ions across cellular membranes. To gain insight into the determinants of ion selectivity, we have determined the crystal structure of a close prokaryotic homolog of the family. The SLC11 transporters were found to share a molecular scaffold observed previously in several different transporters of unrelated sequence. A conserved central binding site was identified that provided the molecular basis for selective absorbtion of iron in the duodenum.
Work from the Dutzler lab in collaboration with the Steyaert laboratory.
Ehrnstorfer et al., 2014

Substrate-binding protein imposed unidirectional secondary transport.

The direction of solute transport by secondary transport proteins depends on the substrate gradients and is by definition bidirectional. Here we detail the functional characterization of a substrate-binding protein (SBP)-dependent secondary transporter. Transport depended critically on the presence of the SBP and was, in contrast to conventional secondary transporters, unidirectional. Reversal of the direction was found to be possible exclusively in the presence of an excess unliganded SBP, a situation unlikely to occur under physiological conditions.
Work from the Poolman lab in collaboration with the Thomas laboratory.
Mulligan and Geertsma et al., 2009