Crystal structures of the Burkholderia multivorans hopanoid transporter HpnN

Kumar, Nitin; Su, Chih-Chia; Chou, Tsung-Han; Radhakrishnan, Abhijith; Delmar, Jared A.; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

doi:10.1073/pnas.1619660114

Crystal structures of the Burkholderia multivorans hopanoid transporter HpnN

Journal Article · Mon Jun 05 00:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1619660114· OSTI ID:1374632

Kumar, Nitin ^[1]; Su, Chih-Chia ^[1]; Chou, Tsung-Han ^[1]; Radhakrishnan, Abhijith ^[1]; Delmar, Jared A. ^[1]; Rajashankar, Kanagalaghatta R. ^[2]; Yu, Edward W. ^[1]

Iowa State Univ., Ames, IA (United States)
Argonne National Lab. (ANL), Argonne, IL (United States); Cornell Univ., Ithaca, NY (United States)

Strains of the Burkholderia cepacia complex (Bcc) are Gram-negative opportunisitic bacteria that are capable of causing serious diseases, mainly in immunocompromised individuals. Bcc pathogens are intrinsically resistant to multiple antibiotics, including β-lactams, aminoglycosides, fluoroquinolones, and polymyxins. They are major pathogens in patients with cystic fibrosis (CF) and can cause severe necrotizing pneumonia, which is often fatal. Hopanoid biosynthesis is one of the major mechanisms involved in multiple antimicrobial resistance of Bcc pathogens. Here, the hpnN gene of B. multivorans encodes an integral membrane protein of the HpnN family of transporters, which is responsible for shuttling hopanoids to the outer membrane. Here, we report crystal structures of B. multivorans HpnN, revealing a dimeric molecule with an overall butterfly shape. Each subunit of the transporter contains 12 transmembrane helices and two periplasmic loops that suggest a plausible pathway for substrate transport. Further analyses indicate that HpnN is capable of shuttling hopanoid virulence factors from the outer leaflet of the inner membrane to the periplasm. Taken together, our data suggest that the HpnN transporter is critical for multidrug resistance and cell wall remodeling in Burkholderia.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); NIH

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1374632

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 25 Vol. 114; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
Burkholderia multivorans
HpnN transporter
cell wall remodeling
hopanoid transport
multidrug resistance

Crystal structures of the Burkholderia multivorans hopanoid transporter HpnN

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