Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa

Akama, Hiroyuki; Matsuura, Takanori; Kashiwagi, Sachiko; Yoneyama, Hiroshi; Narita, Shin-ichiro; Tsukihara, Tomitake; Nakagawa, Atushi; Nakae, Taiji

doi:https://doi.org/10.1074/jbc.C400164200

Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa

Akama, Hiroyuki; Matsuura, Takanori; Kashiwagi, Sachiko et al.

Journal of Biological Chemistry, 2004, 279(25), 25939-25942

Number of Access:912（2025-08-14 01:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/73649

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Title	Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa
Creator	CreatorName Akama, Hiroyuki
	CreatorName Matsuura, Takanori
	CreatorName Kashiwagi, Sachiko
	NRID 1000010220774 1000010220774 CreatorName Yoneyama, Hiroshi
	NRID 1000030338751 1000030338751 CreatorName Narita, Shin-ichiro
	NRID 1000000032277 1000000032277 CreatorName Tsukihara, Tomitake
	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, Takanori Matsuura, Sachiko Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Tomitake Tsukihara, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. Journal of Biological Chemistry. 2004; 279, 25939-25942. © the American Society for Biochemistry and Molecular Biology.
Abstract	The MexAB-OprM efflux pump of Pseudomonas aeruginosa is central to multidrug resistance of this organism, which infects immunocompromised hospital patients. The MexA, MexB, and OprM subunits were assumed to function as the membrane fusion protein, the body of the transporter, and the outer membrane channel protein, respectively. For better understanding of this important xenobiotic transporter, we show the xray crystallographic structure of MexA at a resolution of 2.40 Å. The global MexA structure showed unforeseen new features with a spiral assembly of six and seven protomers that were joined together at one end by a pseudo 2-fold image. The protomer showed a new protein structure with a tandem arrangement consisting of at least three domains and presumably one more. The rod domain had a long hairpin of twisted coiled-coil that extended to one end. The second domain adjacent to the rod α-helical domain was globular and constructed by a cluster of eight short β-sheets. The third domain located distal to the α-helical rod was globular and composed of seven short β-sheets and one short α-helix. The 13-mer was shaped like a woven rattan cylinder with a large internal tubular space and widely opened flared ends. The 6-mer and 7-mer had a funnel-like structure consisting of a tubular rod at one side and a widely opened flared funnel top at the other side. Based on these results, we constructed a model of the MexAB-OprM pump assembly. The three pairs of MexA dimers interacted with the periplasmic α-barrel domain of OprM via the α-helical hairpin, the second domain interacted with both MexB and OprM at their contact site, and the third and disordered domains probably interacted with the distal domain of MexB. In this fashion, the MexA subunit connected MexB and OprM, indicating that MexA is the membrane bridge protein.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	279(25)
Page	25939-25942
Date of Issued	2004-06
Language	English
Handle URL	https://hdl.handle.net/11094/73649
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.C400164200
Relation.isIdenticalTo	PMID 15117957
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(25), p. 25939-25942
DC.title	Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa
DC.creator	Akama, Hiroyuki
	Matsuura, Takanori
	Kashiwagi, Sachiko
	Yoneyama, Hiroshi
	Narita, Shin-ichiro
	Tsukihara, Tomitake
	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	2004-06
DC.identifier	https://doi.org/10.1074/jbc.C400164200
DC.description	This research was originally published in Journal of Biological Chemistry. Hiroyuki Akama, Takanori Matsuura, Sachiko Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Tomitake Tsukihara, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. Journal of Biological Chemistry. 2004; 279, 25939-25942. © the American Society for Biochemistry and Molecular Biology.
DCTERMS.abstract	The MexAB-OprM efflux pump of Pseudomonas aeruginosa is central to multidrug resistance of this organism, which infects immunocompromised hospital patients. The MexA, MexB, and OprM subunits were assumed to function as the membrane fusion protein, the body of the transporter, and the outer membrane channel protein, respectively. For better understanding of this important xenobiotic transporter, we show the xray crystallographic structure of MexA at a resolution of 2.40 Å. The global MexA structure showed unforeseen new features with a spiral assembly of six and seven protomers that were joined together at one end by a pseudo 2-fold image. The protomer showed a new protein structure with a tandem arrangement consisting of at least three domains and presumably one more. The rod domain had a long hairpin of twisted coiled-coil that extended to one end. The second domain adjacent to the rod α-helical domain was globular and constructed by a cluster of eight short β-sheets. The third domain located distal to the α-helical rod was globular and composed of seven short β-sheets and one short α-helix. The 13-mer was shaped like a woven rattan cylinder with a large internal tubular space and widely opened flared ends. The 6-mer and 7-mer had a funnel-like structure consisting of a tubular rod at one side and a widely opened flared funnel top at the other side. Based on these results, we constructed a model of the MexAB-OprM pump assembly. The three pairs of MexA dimers interacted with the periplasmic α-barrel domain of OprM via the α-helical hairpin, the second domain interacted with both MexB and OprM at their contact site, and the third and disordered domains probably interacted with the distal domain of MexB. In this fashion, the MexA subunit connected MexB and OprM, indicating that MexA is the membrane bridge protein.
DC.rights	© the American Society for Biochemistry and Molecular Biology.
DC.format	73649
citation_title	Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa
citation_author	Akama, Hiroyuki
	Matsuura, Takanori
	Kashiwagi, Sachiko
	Yoneyama, Hiroshi
	Narita, Shin-ichiro
	Tsukihara, Tomitake
	Nakagawa, Atushi
	Nakae, Taiji
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2004-06
citation_journal_title	Journal of Biological Chemistry
citation_volume	279
citation_issue	25
citation_firstpage	25939
citation_lastpage	25942
citation_doi	https://doi.org/10.1074/jbc.C400164200
citation_pmid	15117957
citation_public_url	https://hdl.handle.net/11094/73649

Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa

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