Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end

Akama, Hiroyuki; Kanemaki, Misa; Yoshimura, Masato; Tsukihara, Tomitake; Kashiwagi, Tomoe; Yoneyama, Hiroshi; Narita, Shin-ichiro; Nakagawa, Atushi; Nakae, Taiji

doi:https://doi.org/10.1074/jbc.C400445200

Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end

Akama, Hiroyuki; Kanemaki, Misa; Yoshimura, Masato et al.

Journal of Biological Chemistry, 2004, 279(51), 52816-52819

Number of Access:375（2025-06-07 18:07 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/73651

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Title	Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end
Creator	CreatorName Akama, Hiroyuki
	CreatorName Kanemaki, Misa
	CreatorName Yoshimura, Masato
	NRID 1000000032277 1000000032277 CreatorName Tsukihara, Tomitake
	CreatorName Kashiwagi, Tomoe
	NRID 1000010220774 1000010220774 CreatorName Yoneyama, Hiroshi
	NRID 1000030338751 1000030338751 CreatorName Narita, Shin-ichiro
	NRID 1000020188890 1000020188890 ORCID 0000-0002-1700-7861 0000-0002-1700-7861 researchmap permalink atsushi_nakagawa atsushi_nakagawa Scopus Author ID 7202934909 7202934909 CreatorName Nakagawa, Atushi
	NRID 1000050102851 1000050102851 CreatorName Nakae, Taiji
Description	This research was originally published in Journal of Biological Chemistry. Hiroyuki Akama, Misa Kanemaki, Masato Yoshimura, Tomitake Tsukihara, Tomoe Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end. Journal of Biological Chemistry. 2004; 279, 52816-52819. © the American Society for Biochemistry and Molecular Biology.
Abstract	The OprM lipoprotein of Pseudomonas aeruginosa is a member of the MexAB-OprM xenobiotic-antibiotic transporter subunits that is assumed to serve as the drug discharge duct across the outer membrane. The channel structure must differ from that of the porintype open pore because the protein facilitates the exit of antibiotics but not the entry. For better understanding of the structure-function linkage of this important pump subunit, we studied the x-ray crystallographic structure of OprM at the 2.56-Å resolution. The overall structure exhibited trimeric assembly of the OprM monomer that consisted mainly of two domains: the membrane- anchoring β-barrel and the cavity-forming ?α-barrel. OprM anchors the outer membrane by two modes of membrane insertions. One is via the covalently attached NH2-terminal fatty acids and the other is the β-barrel structure consensus on the outer membrane-spanning proteins. The β-barrel had a pore opening with a diameter of about 6–8 Å, which is not large enough to accommodate the exit of any antibiotics. The periplasmic α-barrel was about 100 Å long formed mainly by a bundle of α-helices that formed a solvent-filled cavity of about 25,000 Å3. The proximal end of the cavity was tightly sealed, thereby not permitting the entry of any molecule. The result of this structure was that the resting state of OprM had a small outer membrane pore and a tightly closed periplasmic end, which sounds plausible because the protein should not allow free access of antibiotics. However, these observations raised another unsolved problem about the mechanism of opening of the OprM cavity ends. The crystal structure offers possible mechanisms of pore opening and pump assembly.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	279(51)
Page	52816-52819
Date of Issued	2004-12
Language	English
Handle URL	https://hdl.handle.net/11094/73651
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.C400445200
Relation.isIdenticalTo	PMID 15507433
Access Rights	open access
CopyRight	© the American Society for Biochemistry and Molecular Biology.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2004, 279(51), p. 52816-52819
DC.title	Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end
DC.creator	Akama, Hiroyuki
	Kanemaki, Misa
	Yoshimura, Masato
	Tsukihara, Tomitake
	Kashiwagi, Tomoe
	Yoneyama, Hiroshi
	Narita, Shin-ichiro
	Nakagawa, Atushi
	Nakae, Taiji
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2004-12
DC.identifier	https://doi.org/10.1074/jbc.C400445200
DC.description	This research was originally published in Journal of Biological Chemistry. Hiroyuki Akama, Misa Kanemaki, Masato Yoshimura, Tomitake Tsukihara, Tomoe Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end. Journal of Biological Chemistry. 2004; 279, 52816-52819. © the American Society for Biochemistry and Molecular Biology.
DCTERMS.abstract	The OprM lipoprotein of Pseudomonas aeruginosa is a member of the MexAB-OprM xenobiotic-antibiotic transporter subunits that is assumed to serve as the drug discharge duct across the outer membrane. The channel structure must differ from that of the porintype open pore because the protein facilitates the exit of antibiotics but not the entry. For better understanding of the structure-function linkage of this important pump subunit, we studied the x-ray crystallographic structure of OprM at the 2.56-Å resolution. The overall structure exhibited trimeric assembly of the OprM monomer that consisted mainly of two domains: the membrane- anchoring β-barrel and the cavity-forming ?α-barrel. OprM anchors the outer membrane by two modes of membrane insertions. One is via the covalently attached NH2-terminal fatty acids and the other is the β-barrel structure consensus on the outer membrane-spanning proteins. The β-barrel had a pore opening with a diameter of about 6–8 Å, which is not large enough to accommodate the exit of any antibiotics. The periplasmic α-barrel was about 100 Å long formed mainly by a bundle of α-helices that formed a solvent-filled cavity of about 25,000 Å3. The proximal end of the cavity was tightly sealed, thereby not permitting the entry of any molecule. The result of this structure was that the resting state of OprM had a small outer membrane pore and a tightly closed periplasmic end, which sounds plausible because the protein should not allow free access of antibiotics. However, these observations raised another unsolved problem about the mechanism of opening of the OprM cavity ends. The crystal structure offers possible mechanisms of pore opening and pump assembly.
DC.rights	© the American Society for Biochemistry and Molecular Biology.
DC.format	73651
citation_title	Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end
citation_author	Akama, Hiroyuki
	Kanemaki, Misa
	Yoshimura, Masato
	Tsukihara, Tomitake
	Kashiwagi, Tomoe
	Yoneyama, Hiroshi
	Narita, Shin-ichiro
	Nakagawa, Atushi
	Nakae, Taiji
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2004-12
citation_journal_title	Journal of Biological Chemistry
citation_volume	279
citation_issue	51
citation_firstpage	52816
citation_lastpage	52819
citation_doi	https://doi.org/10.1074/jbc.C400445200
citation_pmid	15507433
citation_public_url	https://hdl.handle.net/11094/73651

Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end

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