1gaj
From Proteopedia
(New page: 200px<br /><applet load="1gaj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gaj, resolution 2.50Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1gaj.gif|left|200px]]<br /><applet load="1gaj" size=" | + | [[Image:1gaj.gif|left|200px]]<br /><applet load="1gaj" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1gaj, resolution 2.50Å" /> | caption="1gaj, resolution 2.50Å" /> | ||
'''CRYSTAL STRUCTURE OF A NUCLEOTIDE-FREE ATP-BINDING CASSETTE FROM AN ABC TRANSPORTER'''<br /> | '''CRYSTAL STRUCTURE OF A NUCLEOTIDE-FREE ATP-BINDING CASSETTE FROM AN ABC TRANSPORTER'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: ATP binding cassette (ABC) transporters are ubiquitously | + | BACKGROUND: ATP binding cassette (ABC) transporters are ubiquitously distributed transmembrane solute pumps that play a causative role in numerous diseases. Previous structures have defined the fold of the ABC and established the flexibility of its alpha-helical subdomain. But the nature of the mechanical changes that occur at each step of the chemical ATPase cycle have not been defined. RESULTS: Crystal structures were determined of the MJ1267 ABC from Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison of these structures reveals an induced-fit effect at the active site likely to be a consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop following the Walker B moves toward the Walker A (P-loop) coupled to backbone conformational changes in the intervening "H-loop", which contains an invariant histidine. These changes affect the region believed to mediate intercassette interaction in the ABC transporter complex. Comparison of the Mg-ADP-bound structure of MJ1267 to the ATP-bound structure of HisP suggests that an outward rotation of the alpha-helical subdomain is coupled to the loss of a molecular contact between the gamma-phosphate of ATP and an invariant glutamine in a segment connecting this subdomain to the core of the cassette. CONCLUSIONS: The induced-fit effect and rotation of the alpha-helical subdomain may play a role in controlling the nucleotide-dependent change in cassette-cassette interaction affinity believed to represent the power-stroke of ABC transporters. Outward rotation of the alpha-helical subdomain also likely facilitates Mg-ADP release after hydrolysis. The MJ1267 structures therefore define features of the nucleotide-dependent conformational changes that drive transmembrane transport in ABC transporters. |
==About this Structure== | ==About this Structure== | ||
| - | 1GAJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with SO4, CL, TBU and PEG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1GAJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=TBU:'>TBU</scene> and <scene name='pdbligand=PEG:'>PEG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GAJ OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Methanocaldococcus jannaschii]] | [[Category: Methanocaldococcus jannaschii]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Dai, P | + | [[Category: Dai, P L.]] |
| - | [[Category: Hunt, J | + | [[Category: Hunt, J F.]] |
[[Category: Karpowich, N.]] | [[Category: Karpowich, N.]] | ||
[[Category: Martsinkevich, O.]] | [[Category: Martsinkevich, O.]] | ||
[[Category: Millen, L.]] | [[Category: Millen, L.]] | ||
| - | [[Category: Thomas, P | + | [[Category: Thomas, P J.]] |
| - | [[Category: Yuan, Y | + | [[Category: Yuan, Y R.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: PEG]] | [[Category: PEG]] | ||
| Line 29: | Line 29: | ||
[[Category: nucleotide-binding domain]] | [[Category: nucleotide-binding domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:47:58 2008'' |
Revision as of 10:48, 21 February 2008
|
CRYSTAL STRUCTURE OF A NUCLEOTIDE-FREE ATP-BINDING CASSETTE FROM AN ABC TRANSPORTER
Overview
BACKGROUND: ATP binding cassette (ABC) transporters are ubiquitously distributed transmembrane solute pumps that play a causative role in numerous diseases. Previous structures have defined the fold of the ABC and established the flexibility of its alpha-helical subdomain. But the nature of the mechanical changes that occur at each step of the chemical ATPase cycle have not been defined. RESULTS: Crystal structures were determined of the MJ1267 ABC from Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison of these structures reveals an induced-fit effect at the active site likely to be a consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop following the Walker B moves toward the Walker A (P-loop) coupled to backbone conformational changes in the intervening "H-loop", which contains an invariant histidine. These changes affect the region believed to mediate intercassette interaction in the ABC transporter complex. Comparison of the Mg-ADP-bound structure of MJ1267 to the ATP-bound structure of HisP suggests that an outward rotation of the alpha-helical subdomain is coupled to the loss of a molecular contact between the gamma-phosphate of ATP and an invariant glutamine in a segment connecting this subdomain to the core of the cassette. CONCLUSIONS: The induced-fit effect and rotation of the alpha-helical subdomain may play a role in controlling the nucleotide-dependent change in cassette-cassette interaction affinity believed to represent the power-stroke of ABC transporters. Outward rotation of the alpha-helical subdomain also likely facilitates Mg-ADP release after hydrolysis. The MJ1267 structures therefore define features of the nucleotide-dependent conformational changes that drive transmembrane transport in ABC transporters.
About this Structure
1GAJ is a Single protein structure of sequence from Methanocaldococcus jannaschii with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter., Karpowich N, Martsinkevich O, Millen L, Yuan YR, Dai PL, MacVey K, Thomas PJ, Hunt JF, Structure. 2001 Jul 3;9(7):571-86. PMID:11470432
Page seeded by OCA on Thu Feb 21 12:47:58 2008
