Structural Changes during Cysteine Desulfurase CsdA and Sulfur Acceptor CsdE Interactions Provide Insight into the trans-Persulfuration

Abstract

Background: Cysteine desulfurases deliver sulfur from cysteine to sulfur acceptors for sulfur utilization in various biological processes. Results: The crystal structure of CsdA-CsdE invokes a unique binding mode compared with other cysteine desulfurase and sulfur acceptor complexes. Conclusion: Conformational flexibility is pronounced only in the region of CsdE during the sulfur transfer interaction. Significance: This structure marks the first complex structure between CsdA/SufS-type cysteine desulfurase and the sulfur acceptor.

Escherichia coli SufE Sulfur Transfer Protein Modulates the SufS Cysteine Desulfurase through Allosteric Conformational Dynamics

“…Based on the CsdA apo -CsdE apo co-structure, it was proposed that residues within 343-354 (helix 16 ), 355-378 (the Cys-364 loop), and 393-406 (helix 18 ) of SufS apo form hydrogen bonds and van der Waals interactions with SufE apo (31). Our HDX trapping data agree that SufS residues within 356 -366 (the Cys-364 loop) are involved in the interaction with SufE (Fig.…”

“…HDX-MS time course experiments reveal that carbamidomethylation of SufE yields increased solvent accessibility and dynamics around Cys-51. 4 A loss of hydrogen bonding with increased backbone solvent accessibility suggests that alkylation of SufE triggers a conformational switch in the loop that could mimic the "sulfur-accepting" state, possibly by forcing the modified Cys-51 side chain out of its groove and into an exposed conformation (31). This interpretation is supported by previous studies showing that SufE alk is a potent inhibitor of SufS enhancement by SufE apo (10).…”

“…Despite the change in CsdE apo conformation, there were no noticeable structural changes to the CsdA apo cysteine desulfurase backbone in the CsdA apo -CsdE apo complex (31). This is in contrast to our HDX-MS studies with SufS apo that showed altered deuterium uptake for two active site peptides, residues 225-236 and 356 -366, in the presence of SufE apo (Fig.…”

“…Our SufE apo HDX data show that the Cys-51 loop is moderately solventaccessible and that binding to SufS apo decreased its backbone dynamics. A recent crystallographic structure of a complex between two E. coli proteins related to SufS and SufE, CsdA and CsdE, is consistent with the conformational change and dynamic stabilization we observed for the Cys-51 loop (PDB: 4LW4) (31). In the CsdA apo -CsdE apo co-structure, the CsdE Cys-61 loop region underwent an ϳ11 Å shift upon interaction with CsdA.…”

“…S1). Given the variety of binding modes between cysteine desulfurases and sulfur acceptors such as CsdA-CsdE, IscS-IscU, and IscS-TusA systems, it is not unreasonable that the SufS apo and SufE apo interaction may not be completely analogous to that of the CsdA-CsdE complex (31,35). We propose that SufE apo binding at or near His-362 and Met-366 on the surface of SufS apo leads to subtle changes in hydrogen bonding or solvent accessibility of backbone amides as manifested by the limited HDX SufE apo "footprint" observed.…”