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| - | {{STRUCTURE_3kbu| PDB=3kbu | SCENE= }}
| + | ==Crystal structure of the ankyrin binding domain of human erythroid beta spectrin (repeats 13-15) in complex with the spectrin binding domain of human erythroid ankyrin (ZU5-ANK), EMTS derivative== |
| - | ===Crystal structure of the ankyrin binding domain of human erythroid beta spectrin (repeats 13-15) in complex with the spectrin binding domain of human erythroid ankyrin (ZU5-ANK), EMTS derivative===
| + | <StructureSection load='3kbu' size='340' side='right' caption='[[3kbu]], [[Resolution|resolution]] 2.75Å' scene=''> |
| - | {{ABSTRACT_PUBMED_20101027}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[3kbu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KBU FirstGlance]. <br> |
| | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene></td></tr> |
| | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kbt|3kbt]], [[3f57|3f57]], [[3edu|3edu]], [[3edv|3edv]], [[3f59|3f59]], [[1u4q|1u4q]]</td></tr> |
| | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPTB, SPTB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ANK, ANK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kbu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kbu RCSB], [http://www.ebi.ac.uk/pdbsum/3kbu PDBsum]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/SPTB1_HUMAN SPTB1_HUMAN]] Defects in SPTB are the cause of elliptocytosis type 3 (EL3) [MIM:[http://omim.org/entry/182870 182870]]. EL3 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.<ref>PMID:8226774</ref> <ref>PMID:7883966</ref> <ref>PMID:8018926</ref> <ref>PMID:1975598</ref> Defects in SPTB are the cause of spherocytosis type 2 (SPH2) [MIM:[http://omim.org/entry/182870 182870]]; also known as hereditary spherocytosis type 2 (HS2). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH2 is characterized by severe hemolytic anemia. Inheritance is autosomal dominant. [[http://www.uniprot.org/uniprot/ANK1_HUMAN ANK1_HUMAN]] Defects in ANK1 are a cause of spherocytosis type 1 (SPH1) [MIM:[http://omim.org/entry/182900 182900]]; also called hereditary spherocytosis type 1 (HS1). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Inheritance can be autosomal dominant or recessive.<ref>PMID:8640229</ref> <ref>PMID:11102985</ref> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/SPTB1_HUMAN SPTB1_HUMAN]] Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane. [[http://www.uniprot.org/uniprot/ANK1_HUMAN ANK1_HUMAN]] Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.<ref>PMID:12456646</ref> Isoform Mu17 together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.<ref>PMID:12456646</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/3kbu_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Maintenance of membrane integrity and organization in the metazoan cell is accomplished through intracellular tethering of membrane proteins to an extensive, flexible protein network. Spectrin, the principal component of this network, is anchored to membrane proteins through the adaptor protein ankyrin. To elucidate the atomic basis for this interaction, we determined a crystal structure of human betaI-spectrin repeats 13 to 15 in complex with the ZU5-ANK domain of human ankyrin R. The structure reveals the role of repeats 14 to 15 in binding, the electrostatic and hydrophobic contributions along the interface, and the necessity for a particular orientation of the spectrin repeats. Using structural and biochemical data as a guide, we characterized the individual proteins and their interactions by binding and thermal stability analyses. In addition to validating the structural model, these data provide insight into the nature of some mutations associated with cell morphology defects, including those found in human diseases such as hereditary spherocytosis and elliptocytosis. Finally, analysis of the ZU5 domain suggests it is a versatile protein-protein interaction module with distinct interaction surfaces. The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain. |
| | | | |
| - | ==Disease==
| + | Structural basis for spectrin recognition by ankyrin.,Ipsaro JJ, Mondragon A Blood. 2010 May 20;115(20):4093-101. Epub 2010 Jan 25. PMID:20101027<ref>PMID:20101027</ref> |
| - | [[http://www.uniprot.org/uniprot/SPTB1_HUMAN SPTB1_HUMAN]] Defects in SPTB are the cause of elliptocytosis type 3 (EL3) [MIM:[http://omim.org/entry/182870 182870]]. EL3 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.<ref>PMID:8226774</ref><ref>PMID:7883966</ref><ref>PMID:8018926</ref><ref>PMID:1975598</ref> Defects in SPTB are the cause of spherocytosis type 2 (SPH2) [MIM:[http://omim.org/entry/182870 182870]]; also known as hereditary spherocytosis type 2 (HS2). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH2 is characterized by severe hemolytic anemia. Inheritance is autosomal dominant. [[http://www.uniprot.org/uniprot/ANK1_HUMAN ANK1_HUMAN]] Defects in ANK1 are a cause of spherocytosis type 1 (SPH1) [MIM:[http://omim.org/entry/182900 182900]]; also called hereditary spherocytosis type 1 (HS1). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Inheritance can be autosomal dominant or recessive.<ref>PMID:8640229</ref><ref>PMID:11102985</ref>
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://www.uniprot.org/uniprot/SPTB1_HUMAN SPTB1_HUMAN]] Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane. [[http://www.uniprot.org/uniprot/ANK1_HUMAN ANK1_HUMAN]] Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.<ref>PMID:12456646</ref> Isoform Mu17 together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.<ref>PMID:12456646</ref>
| + | </div> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | [[3kbu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KBU OCA].
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Ankyrin|Ankyrin]] | | *[[Ankyrin|Ankyrin]] |
| | *[[Spectrin|Spectrin]] | | *[[Spectrin|Spectrin]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:020101027</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ipsaro, J J.]] | + | [[Category: Ipsaro, J J]] |
| - | [[Category: Mondragon, A.]] | + | [[Category: Mondragon, A]] |
| | [[Category: Actin capping]] | | [[Category: Actin capping]] |
| | [[Category: Actin-binding]] | | [[Category: Actin-binding]] |
| Structural highlights
3kbu is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 3kbt, 3f57, 3edu, 3edv, 3f59, 1u4q |
| Gene: | SPTB, SPTB1 (Homo sapiens), ANK, ANK1 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[SPTB1_HUMAN] Defects in SPTB are the cause of elliptocytosis type 3 (EL3) [MIM:182870]. EL3 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.[1] [2] [3] [4] Defects in SPTB are the cause of spherocytosis type 2 (SPH2) [MIM:182870]; also known as hereditary spherocytosis type 2 (HS2). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH2 is characterized by severe hemolytic anemia. Inheritance is autosomal dominant. [ANK1_HUMAN] Defects in ANK1 are a cause of spherocytosis type 1 (SPH1) [MIM:182900]; also called hereditary spherocytosis type 1 (HS1). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Inheritance can be autosomal dominant or recessive.[5] [6]
Function
[SPTB1_HUMAN] Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane. [ANK1_HUMAN] Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.[7] Isoform Mu17 together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.[8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Maintenance of membrane integrity and organization in the metazoan cell is accomplished through intracellular tethering of membrane proteins to an extensive, flexible protein network. Spectrin, the principal component of this network, is anchored to membrane proteins through the adaptor protein ankyrin. To elucidate the atomic basis for this interaction, we determined a crystal structure of human betaI-spectrin repeats 13 to 15 in complex with the ZU5-ANK domain of human ankyrin R. The structure reveals the role of repeats 14 to 15 in binding, the electrostatic and hydrophobic contributions along the interface, and the necessity for a particular orientation of the spectrin repeats. Using structural and biochemical data as a guide, we characterized the individual proteins and their interactions by binding and thermal stability analyses. In addition to validating the structural model, these data provide insight into the nature of some mutations associated with cell morphology defects, including those found in human diseases such as hereditary spherocytosis and elliptocytosis. Finally, analysis of the ZU5 domain suggests it is a versatile protein-protein interaction module with distinct interaction surfaces. The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain.
Structural basis for spectrin recognition by ankyrin.,Ipsaro JJ, Mondragon A Blood. 2010 May 20;115(20):4093-101. Epub 2010 Jan 25. PMID:20101027[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sahr KE, Coetzer TL, Moy LS, Derick LH, Chishti AH, Jarolim P, Lorenzo F, Miraglia del Giudice E, Iolascon A, Gallanello R, et al.. Spectrin cagliari. an Ala-->Gly substitution in helix 1 of beta spectrin repeat 17 that severely disrupts the structure and self-association of the erythrocyte spectrin heterodimer. J Biol Chem. 1993 Oct 25;268(30):22656-62. PMID:8226774
- ↑ Gallagher PG, Weed SA, Tse WT, Benoit L, Morrow JS, Marchesi SL, Mohandas N, Forget BG. Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene. J Clin Invest. 1995 Mar;95(3):1174-82. PMID:7883966 doi:http://dx.doi.org/10.1172/JCI117766
- ↑ Parquet N, Devaux I, Boulanger L, Galand C, Boivin P, Lecomte MC, Dhermy D, Garbarz M. Identification of three novel spectrin alpha I/74 mutations in hereditary elliptocytosis: further support for a triple-stranded folding unit model of the spectrin heterodimer contact site. Blood. 1994 Jul 1;84(1):303-8. PMID:8018926
- ↑ Tse WT, Lecomte MC, Costa FF, Garbarz M, Feo C, Boivin P, Dhermy D, Forget BG. Point mutation in the beta-spectrin gene associated with alpha I/74 hereditary elliptocytosis. Implications for the mechanism of spectrin dimer self-association. J Clin Invest. 1990 Sep;86(3):909-16. PMID:1975598 doi:http://dx.doi.org/10.1172/JCI114792
- ↑ Eber SW, Gonzalez JM, Lux ML, Scarpa AL, Tse WT, Dornwell M, Herbers J, Kugler W, Ozcan R, Pekrun A, Gallagher PG, Schroter W, Forget BG, Lux SE. Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. Nat Genet. 1996 Jun;13(2):214-8. PMID:8640229 doi:10.1038/ng0696-214
- ↑ Leite RC, Basseres DS, Ferreira JS, Alberto FL, Costa FF, Saad ST. Low frequency of ankyrin mutations in hereditary spherocytosis: identification of three novel mutations. Hum Mutat. 2000 Dec;16(6):529. PMID:11102985 doi:<529::AID-HUMU13>3.0.CO;2-N 10.1002/1098-1004(200012)16:6<529::AID-HUMU13>3.0.CO;2-N
- ↑ Michaely P, Tomchick DR, Machius M, Anderson RG. Crystal structure of a 12 ANK repeat stack from human ankyrinR. EMBO J. 2002 Dec 2;21(23):6387-96. PMID:12456646
- ↑ Michaely P, Tomchick DR, Machius M, Anderson RG. Crystal structure of a 12 ANK repeat stack from human ankyrinR. EMBO J. 2002 Dec 2;21(23):6387-96. PMID:12456646
- ↑ Ipsaro JJ, Mondragon A. Structural basis for spectrin recognition by ankyrin. Blood. 2010 May 20;115(20):4093-101. Epub 2010 Jan 25. PMID:20101027 doi:10.1182/blood-2009-11-255604
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