Wiskott-Aldrich syndrome protein

From Proteopedia
Jump to navigation Jump to search

Function

Wiskott-Aldrich syndrome protein (WASP) is involved in nucleating of new F-actin. In the autoinhibited form of WASP a region of the N-terminal interacts with a region of its C-terminal. This interaction is disrupted by CDC42 and phosphatidylinositol 4,5-bisphosphate (PIP2) resulting in the active WASP. WASP domains include EVH1 domain in the N-terminal which bind proline-rich sequences in the WASP-interacting proteins; WH2 domain is ca. 18 residues long and interacts with actin; CRIB or GTPase-binding domain which interacts with CDC42.

  • N-WASP (Neural WASP) belongs to the WASP family of proteins. Human N-WASP stimulates the actin-nucleating activity[1].
  • WAVE-1 facilitates neuronal actin remodeling[2].
  • WAVE-2 facilitates cytoskeletal actin remodeling[3].

Relevance

N-WASP induces actin polymerization in the Shigella bacterium[4]. This bacterium causes dysentery.

Disease

Mutations in WASP can cause Wiskott-Aldrich syndrome which is a rare inherited disease characterized by immune disregulation[5].

3D Structures of Wiskott-Aldrich syndrome protein

Wiskott-Aldrich syndrome protein 3D structures

References

  1. Westerberg LS, Dahlberg C, Baptista M, Moran CJ, Detre C, Keszei M, Eston MA, Alt FW, Terhorst C, Notarangelo LD, Snapper SB. Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function. Blood. 2012 Apr 26;119(17):3966-74. doi: 10.1182/blood-2010-09-308197. Epub 2012 , Mar 12. PMID:22411869 doi:http://dx.doi.org/10.1182/blood-2010-09-308197
  2. Soderling SH, Guire ES, Kaech S, White J, Zhang F, Schutz K, Langeberg LK, Banker G, Raber J, Scott JD. A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. J Neurosci. 2007 Jan 10;27(2):355-65. PMID:17215396 doi:10.1523/JNEUROSCI.3209-06.2006
  3. Nolz JC, Gomez TS, Zhu P, Li S, Medeiros RB, Shimizu Y, Burkhardt JK, Freedman BD, Billadeau DD. The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr Biol. 2006 Jan 10;16(1):24-34. PMID:16401421 doi:10.1016/j.cub.2005.11.036
  4. Suzuki T, Mimuro H, Suetsugu S, Miki H, Takenawa T, Sasakawa C. Neural Wiskott-Aldrich syndrome protein (N-WASP) is the specific ligand for Shigella VirG among the WASP family and determines the host cell type allowing actin-based spreading. Cell Microbiol. 2002 Apr;4(4):223-33. PMID:11952639
  5. Notarangelo LD, Miao CH, Ochs HD. Wiskott-Aldrich syndrome. Curr Opin Hematol. 2008 Jan;15(1):30-6. PMID:18043243 doi:http://dx.doi.org/10.1097/MOH.0b013e3282f30448

Human WASP WH2 domain (pink) complex with α-actin (grey), DNAse I (green), ATP, Ca+2 and Mg+2 ions, glycerol and formic acid (PDB code 2a3z)

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky