Biology subjects

Straub, M. S.

Publications and source records attributed to Straub, M. S..

3 recordsLinked to original sources

bioRxiv2022

Structural and functional properties of a plant NRAMP related aluminum transporter

The transport of transition metal ions by members of the SLC11/NRAMP family constitutes a ubiquitous mechanism for the uptake of Fe2+ and Mn2+ across all kingdoms of life. Despite the strong conservation of the family, two of its branches have evolved a distinct substrate preference with one mediating Mg2+ uptake in prokaryotes and another the transport of Al3+ into plant cells. Our previous work on the SLC11 transporter from Eggerthella lenta revealed the basis for its Mg2+ selectivity (Ramanadane et al., 2022). Here we have addressed the structural and functional properties of a putative Al3+ transporter from Setaria italica. We show that the protein transports diverse divalent metal ions and binds the trivalent ions Al3+ and Ga3+, which are both presumable substrates. Its cryo-EM structure displays an occluded conformation that is closer to an inward-than an outward-facing state with a binding site that is remodeled to accommodate the increased charge density of its transported substrate.

biophysics↗

bioRxiv2021

Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

Members of the ubiquitous SLC11/NRAMP family catalyze the uptake of divalent transition metal ions into cells. They have evolved to efficiently select these trace elements from a large pool of Ca2+ and Mg2+, which are both orders of magnitude more abundant, and to concentrate them in the cytoplasm aided by the cotransport of H+ serving as energy source. In the present study, we have characterized a member of a distant clade of the family found in prokaryotes, termed NRMTs, that were proposed to function as transporters of Mg2+. The protein transports Mg2+ and Mn2+ but not Ca2+ by a mechanism that is not coupled to H+. Structures determined by cryo-EM and X-ray crystallography revealed a generally similar protein architecture compared to classical NRAMPs, with a restructured ion binding site whose increased volume provides suitable interactions with ions that likely have retained much of their hydration shell.

biophysics↗

bioRxiv2021

Cryo-EM structures of the Caspase activated protein XKR9 involved in apoptotic lipid scrambling

The exposure of the negatively charged lipid phosphatidylserine on the cell-surface, catalyzed by lipid scramblases, is an important signal for the clearance of apoptotic cells by macrophages. The protein XKR9 is a member of a conserved family that has been associated with apoptotic lipid scrambling. Here, we describe structures of full-length and caspase-treated XKR9 in complex with a synthetic nanobody determined by cryo-electron microscopy. The 43 kDa monomeric membrane protein contains eight membrane-spanning helices, two segments that are partly inserted into the lipid bilayer and is organized as two structurally related repeats. In the full-length protein, the C-terminus interacts with a hydrophobic site located at the intracellular side acting as an inhibitor of protein function. Cleavage by caspase-3 at a specific site releases 16 residues of the C-terminus thus making the binding site accessible to the cytoplasm. Collectively, the work has revealed the unknown architecture of the XKR family and has provided initial insight into its activation by caspases.

biophysics↗