Structure of an orthorhombic crystal form of human cytosolic aconitase (IRP1)
Structural highlights
2b3x is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
ACOHC_HUMAN Bifunctional iron sensor that switches between 2 activities depending on iron availability (PubMed:1946430, PubMed:1281544, PubMed:8041788). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization (PubMed:1946430, PubMed:1281544, PubMed:8041788, PubMed:23891004). Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA (PubMed:1946430, PubMed:1281544, PubMed:8041788, PubMed:23891004).[1][2][3][4] Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.[5][6][7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
↑ Haile DJ, Rouault TA, Harford JB, Kennedy MC, Blondin GA, Beinert H, Klausner RD. Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9. PMID:1281544 doi:10.1073/pnas.89.24.11735
↑ Kaptain S, Downey WE, Tang C, Philpott C, Haile D, Orloff DG, Harford JB, Rouault TA, Klausner RD. A regulated RNA binding protein also possesses aconitase activity. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13. PMID:1946430
↑ Stehling O, Mascarenhas J, Vashisht AA, Sheftel AD, Niggemeyer B, Rösser R, Pierik AJ, Wohlschlegel JA, Lill R. Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins. Cell Metab. 2013 Aug 6;18(2):187-98. PMID:23891004 doi:10.1016/j.cmet.2013.06.015
↑ Philpott CC, Klausner RD, Rouault TA. The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5. PMID:8041788
↑ Haile DJ, Rouault TA, Harford JB, Kennedy MC, Blondin GA, Beinert H, Klausner RD. Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9. PMID:1281544 doi:10.1073/pnas.89.24.11735
↑ Kaptain S, Downey WE, Tang C, Philpott C, Haile D, Orloff DG, Harford JB, Rouault TA, Klausner RD. A regulated RNA binding protein also possesses aconitase activity. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13. PMID:1946430
↑ Philpott CC, Klausner RD, Rouault TA. The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7321-5. PMID:8041788
