View source for 2a41


==Ternary complex of the WH2 Domain of WIP with Actin-DNAse I==
<StructureSection load='2a41' size='340' side='right'caption='[[2a41]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2a41]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A41 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2a3z|2a3z]], [[2a40|2a40]], [[2a42|2a42]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Deoxyribonuclease_I Deoxyribonuclease I], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.21.1 3.1.21.1] </span></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=2a41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a41 OCA], [https://pdbe.org/2a41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a41 RCSB], [https://www.ebi.ac.uk/pdbsum/2a41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a41 ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/WIPF1_HUMAN WIPF1_HUMAN]] Defects in WIPF1 are the cause of Wiskott-Aldrich syndrome type 2 (WAS2) [MIM:[https://omim.org/entry/614493 614493]]. WAS2 is an immunodeficiency disorder characterized by eczema, thrombocytopenia, recurrent infections, defective T-cell proliferation, and impaired natural killer cell function.<ref>PMID:22231303</ref>  
== Function ==
[[https://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[https://www.uniprot.org/uniprot/WIPF1_HUMAN WIPF1_HUMAN]] May have direct activity on the actin cytoskeleton. Induces actin polymerization and redistribution. Contributes with NCK1 and GRB2 in the recruitment and activation of WASL. May participate in regulating the subcellular localization of WASL, resulting in the disassembly of stress fibers in favor of filopodia formation (By similarity). Plays an important role in the intracellular motility of vaccinia virus by functioning as an adapter for recruiting WASL to vaccinia virus.<ref>PMID:9405671</ref> <ref>PMID:10878810</ref>  [[https://www.uniprot.org/uniprot/DNAS1_BOVIN DNAS1_BOVIN]] Among other functions, seems to be involved in cell death by apoptosis. Binds specifically to G-actin and blocks actin polymerization (By similarity). 
== 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/a4/2a41_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=2a41 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) is a small and widespread actin-binding motif. In the WASP family, WH2 plays a role in filament nucleation by Arp2/3 complex. Here we describe the crystal structures of complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares structural similarity with the N-terminal portion of the actin monomer-sequestering thymosin beta domain (Tbeta). We show that both domains inhibit nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a common binding site for many unrelated actin-binding proteins. Importantly, WH2 is significantly shorter than Tbeta but binds actin with approximately 10-fold higher affinity. WH2 lacks a C-terminal extension that in Tbeta4 becomes involved in monomer sequestration by interfering with intersubunit contacts in F-actin. Owing to their shorter length, WH2 domains connected in tandem by short linkers can coexist with intersubunit contacts in F-actin and are proposed to function in filament nucleation by lining up actin subunits along a filament strand. The WH2-central region of WASP-family proteins is proposed to function in an analogous way by forming a special class of tandem repeats whose function is to line up actin and Arp2 during Arp2/3 nucleation. The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation.

Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly.,Chereau D, Kerff F, Graceffa P, Grabarek Z, Langsetmo K, Dominguez R Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16644-9. Epub 2005 Nov 7. PMID:16275905<ref>PMID:16275905</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2a41" style="background-color:#fffaf0;"></div>

==See Also==
*[[Actin 3D structures|Actin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Deoxyribonuclease I]]
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Chereau, D]]
[[Category: Dominguez, R]]
[[Category: Kerff, F]]
[[Category: Actin]]
[[Category: Arp2/3]]
[[Category: Dnase i]]
[[Category: Structural protein]]
[[Category: Wasp]]
[[Category: Wh2]]
[[Category: Wip]]