2qac: Difference between revisions

Revision as of 19:37, 21 February 2008

The closed MTIP-MyosinA-tail complex from the malaria parasite invasion machinery

OverviewOverview

The Myosin A-tail interacting protein (MTIP) of the malaria parasite links the actomyosin motor of the host cell invasion machinery to its inner membrane complex. We report here that at neutral pH Plasmodium falciparum MTIP in complex with Myosin A adopts a compact conformation, with its two domains completely surrounding the Myosin A-tail helix, dramatically different from previously observed extended MTIP structures. Crystallographic and mutagenesis studies show that H810 and K813 of Myosin A are key players in the formation of the compact MTIP:Myosin A complex. Only the unprotonated state of Myosin A-H810 is compatible with the compact complex. Most surprisingly, every side-chain atom of Myosin A-K813 is engaged in contacts with MTIP. While this side-chain was previously considered to prevent a compact conformation of MTIP with Myosin A, it actually appears to be essential for the formation of the compact complex. The hydrophobic pockets and adaptability seen in the available series of MTIP structures bodes well for the discovery of inhibitors of cell invasion by malaria parasites.

About this StructureAbout this Structure

2QAC is a Protein complex structure of sequences from Plasmodium falciparum 3d7. Full crystallographic information is available from OCA.

ReferenceReference

The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery., Bosch J, Turley S, Roach CM, Daly TM, Bergman LW, Hol WG, J Mol Biol. 2007 Sep 7;372(1):77-88. Epub 2007 Jun 9. PMID:17628590

Page seeded by OCA on Thu Feb 21 18:37:37 2008

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 ==Overview==
-The Myosin A-tail interacting protein (MTIP) of the malaria parasite links, the actomyosin motor of the host cell invasion machinery to its inner, membrane complex. We report here that at neutral pH Plasmodium falciparum, MTIP in complex with Myosin A adopts a compact conformation, with its two, domains completely surrounding the Myosin A-tail helix, dramatically, different from previously observed extended MTIP structures., Crystallographic and mutagenesis studies show that H810 and K813 of Myosin, A are key players in the formation of the compact MTIP:Myosin A complex., Only the unprotonated state of Myosin A-H810 is compatible with the, compact complex. Most surprisingly, every side-chain atom of Myosin A-K813, is engaged in contacts with MTIP. While this side-chain was previously, considered to prevent a compact conformation of MTIP with Myosin A, it, actually appears to be essential for the formation of the compact complex., The hydrophobic pockets and adaptability seen in the available series of, MTIP structures bodes well for the discovery of inhibitors of cell, invasion by malaria parasites.
+The Myosin A-tail interacting protein (MTIP) of the malaria parasite links the actomyosin motor of the host cell invasion machinery to its inner membrane complex. We report here that at neutral pH Plasmodium falciparum MTIP in complex with Myosin A adopts a compact conformation, with its two domains completely surrounding the Myosin A-tail helix, dramatically different from previously observed extended MTIP structures. Crystallographic and mutagenesis studies show that H810 and K813 of Myosin A are key players in the formation of the compact MTIP:Myosin A complex. Only the unprotonated state of Myosin A-H810 is compatible with the compact complex. Most surprisingly, every side-chain atom of Myosin A-K813 is engaged in contacts with MTIP. While this side-chain was previously considered to prevent a compact conformation of MTIP with Myosin A, it actually appears to be essential for the formation of the compact complex. The hydrophobic pockets and adaptability seen in the available series of MTIP structures bodes well for the discovery of inhibitors of cell invasion by malaria parasites.
 ==About this Structure==
@@ Line 10: / Line 10: @@
 ==Reference==
-The Closed MTIP-Myosin A-Tail Complex from the Malaria Parasite Invasion Machinery., Bosch J, Turley S, Roach CM, Daly TM, Bergman LW, Hol WG, J Mol Biol. 2007 Sep 7;372(1):77-88. Epub 2007 Jun 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17628590 17628590]
+The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery., Bosch J, Turley S, Roach CM, Daly TM, Bergman LW, Hol WG, J Mol Biol. 2007 Sep 7;372(1):77-88. Epub 2007 Jun 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17628590 17628590]
 [[Category: Plasmodium falciparum 3d7]]
 [[Category: Protein complex]]
-[[Category: Bergman, L.W.]]
+[[Category: Bergman, L W.]]
 [[Category: Bosch, J.]]
-[[Category: Daly, T.M.]]
+[[Category: Daly, T M.]]
-[[Category: Hol, W.G.J.]]
+[[Category: Hol, W G.J.]]
-[[Category: Roach, C.M.]]
+[[Category: Roach, C M.]]
-[[Category: SGPP, Structural.Genomics.of.Pathogenic.Protozoa.Consortium.]]
+[[Category: SGPP, Structural Genomics of Pathogenic Protozoa Consortium.]]
 [[Category: Turley, S.]]
 [[Category: malaria invasion]]
@@ Line 27: / Line 27: @@
 [[Category: structural genomics of pathogenic protozoa consortium]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:43:47 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:37:37 2008''