2a41
From Proteopedia
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|PDB= 2a41 |SIZE=350|CAPTION= <scene name='initialview01'>2a41</scene>, resolution 2.60Å | |PDB= 2a41 |SIZE=350|CAPTION= <scene name='initialview01'>2a41</scene>, resolution 2.60Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand= | + | |LIGAND= <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=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Deoxyribonuclease_I Deoxyribonuclease I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.21.1 3.1.21.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxyribonuclease_I Deoxyribonuclease I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.21.1 3.1.21.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2a3z|2A3Z]], [[2a40|2A40]], [[2a42|2A42]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a41 OCA], [http://www.ebi.ac.uk/pdbsum/2a41 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a41 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605100 605100]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Dominguez, R.]] | [[Category: Dominguez, R.]] | ||
[[Category: Kerff, F.]] | [[Category: Kerff, F.]] | ||
| - | [[Category: ATP]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: FMT]] | ||
| - | [[Category: MG]] | ||
[[Category: actin]] | [[Category: actin]] | ||
[[Category: arp2/3]] | [[Category: arp2/3]] | ||
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[[Category: wip]] | [[Category: wip]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:47:34 2008'' |
Revision as of 22:47, 30 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , , | ||||||
| Activity: | Deoxyribonuclease I, with EC number 3.1.21.1 | ||||||
| Related: | 2A3Z, 2A40, 2A42
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Ternary complex of the WH2 Domain of WIP with Actin-DNAse I
Overview
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.
About this Structure
2A41 is a Protein complex structure of sequences from Bos taurus and Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 01:47:34 2008
Categories: Bos taurus | Deoxyribonuclease I | Oryctolagus cuniculus | Protein complex | Chereau, D. | Dominguez, R. | Kerff, F. | Actin | Arp2/3 | Dnase i | Wasp | Wh2 | Wip
