5F4B

Structure of B. abortus WrbA-related protein A (WrpA)

Summary for 5F4B

• Entry DOI: 10.2210/pdb5f4b/pdb
• Descriptor: NAD(P)H dehydrogenase (quinone), FLAVIN MONONUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: brucella, wrba, nadh:quinone oxidoreductase, tetramer, structural genomics, psi-biology, midwest center for structural genomics, mcsg, oxidoreductase
• Biological source: Brucella abortus (strain 2308)
• Total number of polymer chains: 2
• Total formula weight: 44458.99

Authors

Herrou, J.,Czyz, D.,Willett, J.W.,Kim, H.S.,Chhor, G.,Endres, M.,Babnigg, G.,Kim, Y.,Joachimiak, A.,Crosson, S.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2015-12-03, release date: 2016-03-09, Last modification date: 2024-03-06)

Primary citation

Herrou, J.,Czyz, D.M.,Willett, J.W.,Kim, H.S.,Chhor, G.,Babnigg, G.,Kim, Y.,Crosson, S.
WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System.
J.Bacteriol., 198:1281-1293, 2016

PubMed Abstract: The general stress response (GSR) system of the intracellular pathogen Brucella abortus controls the transcription of approximately 100 genes in response to a range of stress cues. The core genetic regulatory components of the GSR are required for B. abortus survival under nonoptimal growth conditions in vitro and for maintenance of chronic infection in an in vivo mouse model. The functions of the majority of the genes in the GSR transcriptional regulon remain undefined. bab1_1070 is among the most highly regulated genes in this regulon: its transcription is activated 20- to 30-fold by the GSR system under oxidative conditions in vitro. We have solved crystal structures of Bab1_1070 and demonstrate that it forms a homotetrameric complex that resembles those of WrbA-type NADH:quinone oxidoreductases, which are members of the flavodoxin protein family. However, B. abortus WrbA-related protein (WrpA) does not bind flavin cofactors with a high affinity and does not function as an NADH:quinone oxidoreductase in vitro. Soaking crystals with flavin mononucleotide (FMN) revealed a likely low-affinity binding site adjacent to the canonical WrbA flavin binding site. Deletion of wrpA (ΔwrpA) does not compromise cell survival under acute oxidative stress in vitro or attenuate infection in cell-based or mouse models. However, a ΔwrpA strain does elicit increased splenomegaly in a mouse model, suggesting that WrpA modulates B. abortus interaction with its mammalian host. Despite high structural homology with canonical WrbA proteins, we propose that B. abortus WrpA represents a functionally distinct member of the diverse flavodoxin family.

PubMed: 26858101
DOI: 10.1128/JB.00982-15

Experimental method

X-RAY DIFFRACTION (2.498 Å)