3zwh

From Proteopedia

Jump to: navigation, search
3zwh, resolution 1.94Å ()
Ligands: , ,
Related: 1m31


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Ca2+-bound S100A4 C3S, C81S, C86S and F45W mutant complexed with myosin IIA

Publication Abstract from PubMed

S100A4 is a member of the S100 family of calcium-binding proteins that is directly involved in tumor metastasis. It binds to the nonmuscle myosin IIA (NMIIA) tail near the assembly competence domain (ACD) promoting filament disassembly, which could be associated with increasing metastatic potential of tumor cells. Here, we investigate the mechanism of S100A4-NMIIA interaction based on binding studies and the crystal structure of S100A4 in complex with a 45-residue-long myosin heavy chain fragment. Interestingly, we also find that S100A4 binds as strongly to a homologous heavy chain fragment of nonmuscle myosin IIC as to NMIIA. The structure of the S100A4-NMIIA complex reveals a unique mode of interaction in the S100 family: A single, predominantly alpha-helical myosin chain is wrapped around the Ca(2+)-bound S100A4 dimer occupying both hydrophobic binding pockets. Thermal denaturation experiments of coiled-coil forming NMIIA fragments indicate that the coiled-coil partially unwinds upon S100A4 binding. Based on these results, we propose a model for NMIIA filament disassembly: Part of the random coil tailpiece and the C-terminal residues of the coiled-coil are wrapped around an S100A4 dimer disrupting the ACD and resulting in filament dissociation. The description of the complex will facilitate the design of specific drugs that interfere with the S100A4-NMIIA interaction.

Crystal structure of the S100A4-nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism., Kiss B, Duelli A, Radnai L, Kekesi KA, Katona G, Nyitray L, Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6048-53. Epub 2012 Mar 28. PMID:22460785

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

Disease

[MYH9_HUMAN] MYH9-related thrombocytopenia;Autosomal dominant nonsyndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Subjects with mutations in the motor domain of MYH9 present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. The clinical course of patients with mutations in the four most frequently affected residues of MYH9 (responsible for 70% of MYH9-related cases) were evaluated. Mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. Genetic variations in MYH9 are associated with non-diabetic end stage renal disease (ESRD).

Function

[MYH9_HUMAN] Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10.[1]

About this Structure

3zwh is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA.

See Also

Reference

  • Kiss B, Duelli A, Radnai L, Kekesi KA, Katona G, Nyitray L. Crystal structure of the S100A4-nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism. Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6048-53. Epub 2012 Mar 28. PMID:22460785 doi:10.1073/pnas.1114732109
  1. Betapudi V. Myosin II motor proteins with different functions determine the fate of lamellipodia extension during cell spreading. PLoS One. 2010 Jan 5;5(1):e8560. doi: 10.1371/journal.pone.0008560. PMID:20052411 doi:http://dx.doi.org/10.1371/journal.pone.0008560

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools