1mjd

From Proteopedia

(Difference between revisions)

Current revision

Structure of N-terminal domain of human doublecortin

Structural highlights

1mjd is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

DCX_HUMAN Defects in DCX are the cause of lissencephaly X-linked type 1 (LISX1) [MIM:300067; also called X-LIS or LIS. LISX1 is a classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] Defects in DCX are the cause of subcortical band heterotopia X-linked (SBHX) [MIM:300067; also known as double cortex or subcortical laminar heterotopia (SCLH). SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] Note=A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).

Function

DCX_HUMAN Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration.^[15]

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

The doublecortin-like domains (DCX), which typically occur in tandem, are novel microtubule-binding modules. DCX tandems are found in doublecortin, a 360-residue protein expressed in migrating neurons; the doublecortin-like kinase (DCLK); the product of the RP1 gene that is responsible for a form of inherited blindness; and several other proteins. Mutations in the gene encoding doublecortin cause lissencephaly in males and the 'double-cortex syndrome' in females. We here report a solution structure of the N-terminal DCX domain of human doublecortin and a 1.5 A resolution crystal structure of the equivalent domain from human DCLK. Both show a stable, ubiquitin-like tertiary fold with distinct structural similarities to GTPase-binding domains. We also show that the C-terminal DCX domains of both proteins are only partially folded. In functional assays, the N-terminal DCX domain of doublecortin binds only to assembled microtubules, whereas the C-terminal domain binds to both microtubules and unpolymerized tubulin.

The DCX-domain tandems of doublecortin and doublecortin-like kinase.,Kim MH, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh CA, Otlewski J, Bushweller JH, Derewenda ZS Nat Struct Biol. 2003 May;10(5):324-33. PMID:12692530^[16]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ des Portes V, Pinard JM, Billuart P, Vinet MC, Koulakoff A, Carrie A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y, Catala M, Kahn A, Beldjord C, Chelly J. A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell. 1998 Jan 9;92(1):51-61. PMID:9489699
↑ Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA. Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell. 1998 Jan 9;92(1):63-72. PMID:9489700
↑ Sossey-Alaoui K, Hartung AJ, Guerrini R, Manchester DK, Posar A, Puche-Mira A, Andermann E, Dobyns WB, Srivastava AK. Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects. Hum Mol Genet. 1998 Aug;7(8):1327-32. PMID:9668176
↑ Pilz DT, Matsumoto N, Minnerath S, Mills P, Gleeson JG, Allen KM, Walsh CA, Barkovich AJ, Dobyns WB, Ledbetter DH, Ross ME. LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet. 1998 Dec;7(13):2029-37. PMID:9817918
↑ Demelas L, Serra G, Conti M, Achene A, Mastropaolo C, Matsumoto N, Dudlicek LL, Mills PL, Dobyns WB, Ledbetter DH, Das S. Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene. Neurology. 2001 Jul 24;57(2):327-30. PMID:11468322
↑ Aigner L, Uyanik G, Couillard-Despres S, Ploetz S, Wolff G, Morris-Rosendahl D, Martin P, Eckel U, Spranger S, Otte J, Woerle H, Holthausen H, Apheshiotis N, Fluegel D, Winkler J. Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders. Neurology. 2003 Jan 28;60(2):329-32. PMID:12552055
↑ des Portes V, Francis F, Pinard JM, Desguerre I, Moutard ML, Snoeck I, Meiners LC, Capron F, Cusmai R, Ricci S, Motte J, Echenne B, Ponsot G, Dulac O, Chelly J, Beldjord C. doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH). Hum Mol Genet. 1998 Jul;7(7):1063-70. PMID:9618162
↑ Gleeson JG, Minnerath SR, Fox JW, Allen KM, Luo RF, Hong SE, Berg MJ, Kuzniecky R, Reitnauer PJ, Borgatti R, Mira AP, Guerrini R, Holmes GL, Rooney CM, Berkovic S, Scheffer I, Cooper EC, Ricci S, Cusmai R, Crawford TO, Leroy R, Andermann E, Wheless JW, Dobyns WB, Walsh CA, et al.. Characterization of mutations in the gene doublecortin in patients with double cortex syndrome. Ann Neurol. 1999 Feb;45(2):146-53. PMID:9989615
↑ Kato M, Kimura T, Lin C, Ito A, Kodama S, Morikawa T, Soga T, Hayasaka K. A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia. Hum Genet. 1999 Apr;104(4):341-4. PMID:10369164
↑ Pilz DT, Kuc J, Matsumoto N, Bodurtha J, Bernadi B, Tassinari CA, Dobyns WB, Ledbetter DH. Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1. Hum Mol Genet. 1999 Sep;8(9):1757-60. PMID:10441340
↑ Sakamoto M, Ono J, Okada S, Nakamura Y, Kurahashi H. Genetic alteration of the DCX gene in Japanese patients with subcortical laminar heterotopia or isolated lissencephaly sequence. J Hum Genet. 2000;45(3):167-70. PMID:10807542 doi:10.1007/s100380050204
↑ Kato M, Kanai M, Soma O, Takusa Y, Kimura T, Numakura C, Matsuki T, Nakamura S, Hayasaka K. Mutation of the doublecortin gene in male patients with double cortex syndrome: somatic mosaicism detected by hair root analysis. Ann Neurol. 2001 Oct;50(4):547-51. PMID:11601509
↑ Matsumoto N, Leventer RJ, Kuc JA, Mewborn SK, Dudlicek LL, Ramocki MB, Pilz DT, Mills PL, Das S, Ross ME, Ledbetter DH, Dobyns WB. Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia. Eur J Hum Genet. 2001 Jan;9(1):5-12. PMID:11175293 doi:10.1038/sj.ejhg.5200548
↑ D'Agostino MD, Bernasconi A, Das S, Bastos A, Valerio RM, Palmini A, Costa da Costa J, Scheffer IE, Berkovic S, Guerrini R, Dravet C, Ono J, Gigli G, Federico A, Booth F, Bernardi B, Volpi L, Tassinari CA, Guggenheim MA, Ledbetter DH, Gleeson JG, Lopes-Cendes I, Vossler DG, Malaspina E, Franzoni E, Sartori RJ, Mitchell MH, Mercho S, Dubeau F, Andermann F, Dobyns WB, Andermann E. Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females. Brain. 2002 Nov;125(Pt 11):2507-22. PMID:12390976
↑ Slepak TI, Salay LD, Lemmon VP, Bixby JL. Dyrk kinases regulate phosphorylation of doublecortin, cytoskeletal organization, and neuronal morphology. Cytoskeleton (Hoboken). 2012 Jul;69(7):514-27. doi: 10.1002/cm.21021. Epub 2012, Mar 7. PMID:22359282 doi:10.1002/cm.21021
↑ Kim MH, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh CA, Otlewski J, Bushweller JH, Derewenda ZS. The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nat Struct Biol. 2003 May;10(5):324-33. PMID:12692530 doi:10.1038/nsb918

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mjd"

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:1mjd.png|left|200px]]
-<!--
+==Structure of N-terminal domain of human doublecortin==
-The line below this paragraph, containing "STRUCTURE_1mjd", creates the "Structure Box" on the page.
+<StructureSection load='1mjd' size='340' side='right'caption='[[1mjd]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1mjd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MJD FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
--->
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mjd OCA], [https://pdbe.org/1mjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mjd RCSB], [https://www.ebi.ac.uk/pdbsum/1mjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mjd ProSAT]</span></td></tr>
-{{STRUCTURE_1mjd|  PDB=1mjd  |  SCENE=  }}
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/DCX_HUMAN DCX_HUMAN] Defects in DCX are the cause of lissencephaly X-linked type 1 (LISX1) [MIM:[https://omim.org/entry/300067 300067]; also called X-LIS or LIS. LISX1 is a classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.<ref>PMID:9489699</ref> <ref>PMID:9489700</ref> <ref>PMID:9668176</ref> <ref>PMID:9817918</ref> <ref>PMID:11468322</ref> <ref>PMID:12552055</ref>   Defects in DCX are the cause of subcortical band heterotopia X-linked (SBHX) [MIM:[https://omim.org/entry/300067 300067]; also known as double cortex or subcortical laminar heterotopia (SCLH). SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.<ref>PMID:9618162</ref> <ref>PMID:9989615</ref> <ref>PMID:10369164</ref> <ref>PMID:10441340</ref> <ref>PMID:10807542</ref> <ref>PMID:11601509</ref> <ref>PMID:11175293</ref> <ref>PMID:12390976</ref>   Note=A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
+== Function ==
+[https://www.uniprot.org/uniprot/DCX_HUMAN DCX_HUMAN] Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration.<ref>PMID:22359282</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/mj/1mjd_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/main_output.php?pdb_ID=1mjd ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The doublecortin-like domains (DCX), which typically occur in tandem, are novel microtubule-binding modules. DCX tandems are found in doublecortin, a 360-residue protein expressed in migrating neurons; the doublecortin-like kinase (DCLK); the product of the RP1 gene that is responsible for a form of inherited blindness; and several other proteins. Mutations in the gene encoding doublecortin cause lissencephaly in males and the 'double-cortex syndrome' in females. We here report a solution structure of the N-terminal DCX domain of human doublecortin and a 1.5 A resolution crystal structure of the equivalent domain from human DCLK. Both show a stable, ubiquitin-like tertiary fold with distinct structural similarities to GTPase-binding domains. We also show that the C-terminal DCX domains of both proteins are only partially folded. In functional assays, the N-terminal DCX domain of doublecortin binds only to assembled microtubules, whereas the C-terminal domain binds to both microtubules and unpolymerized tubulin.
-===Structure of N-terminal domain of human doublecortin===
+The DCX-domain tandems of doublecortin and doublecortin-like kinase.,Kim MH, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh CA, Otlewski J, Bushweller JH, Derewenda ZS Nat Struct Biol. 2003 May;10(5):324-33. PMID:12692530<ref>PMID:12692530</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_12692530}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1mjd" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 12692530 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_12692530}}
+__TOC__
+</StructureSection>
-==Disease==
-Known disease associated with this structure: Lissencephaly, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300121 300121]], Subcortical laminal heteropia, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300121 300121]]
-==About this Structure==
-MJD is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MJD OCA].
-==Reference==
-The DCX-domain tandems of doublecortin and doublecortin-like kinase., Kim MH, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh CA, Otlewski J, Bushweller JH, Derewenda ZS, Nat Struct Biol. 2003 May;10(5):324-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12692530 12692530]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Bushweller, J H.]]
+[[Category: Bushweller JH]]
-[[Category: Cierpicki, T.]]
+[[Category: Cierpicki T]]
-[[Category: Dauter, Z.]]
+[[Category: Dauter Z]]
-[[Category: Derewenda, U.]]
+[[Category: Derewenda U]]
-[[Category: Derewenda, Z S.]]
+[[Category: Derewenda ZS]]
-[[Category: Devedjiev, Y.]]
+[[Category: Devedjiev Y]]
-[[Category: Feng, Y.]]
+[[Category: Feng Y]]
-[[Category: Kim, M H.]]
+[[Category: Kim MH]]
-[[Category: Krowarsch, D.]]
+[[Category: Krowarsch D]]
-[[Category: Otlewski, J.]]
+[[Category: Otlewski J]]
-[[Category: Walsh, C A.]]
+[[Category: Walsh CA]]
-[[Category: Dcx domain]]
-[[Category: Microtubule associated protein]]
-[[Category: Ubiquitin-like fold]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul  3 00:06:20 2008''

1mjd

From Proteopedia

Current revision

Structure of N-terminal domain of human doublecortin

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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