Disordered Motifs and Domains in Cell Control
Poster Session II
33-POS
Board 9
The Regulation of Non Muscle Myosin II by the Disordered Non-helical Tailpiece
Noa Lahav
1
, Shoshana Ravid
2
, Assaf Friedler
1
.
1
The Hebrew university, Jerusalem, Israel,
2
The Hebrew university-Hadassah Medical School,
Jerusalem, Israel.
Non-muscle myosin II (NMII) mediates cellular processes that require contractility. It is
composed of a globular motor domain in its N-terminal region and a coiled-coil rod domain in
the C-terminal region and undergoes dynamic filament assembly-disassembly cycles to facilitate
its activities. NMII isoform C (NMII-C) has a disordered 55-residue C-terminal tailpiece
(residues 1946-2000), which regulates the filament assembly of NMII-C. The N-terminal region
of the tailpiece (residues 1946-1967) has a net positive charge of +7 while its C-terminal region
(residues 1968-2000) has a net negative charge of -10. We previously demonstrated that a
peptide corresponding to the positive part of the non-helical tailpiece promotes filament
assembly of NMII-C. Phosphorylation of two specific threonine residues (positions 1957 and
1960) in the positively charged region of the tailpiece introduces negative charges with
consequent shift from attraction between NMII-C rods that leads to filament assembly, to
repulsion leading to inhibition of filament assembly. We synthesized phosphorylated peptides
derived from the positively charged region of the tailpiece, in which the relevant threonines were
replaced by phosphothreonines. We found that a single phosphorylation on either of the two
threonines resulted in inhibition of NMII-C
1296-1854
filament assembly. The positively charged
tailpiece
1946-1967
and its derivatives modulate the filament assemble of NMII-C and thus may
serve as lead compounds against diseases resulting from mutations that disrupt the NMII
filament assembly such as cancer.
Refernces:
(1) Ronen, D., & Ravid, S. (2009), J Biol Chem, 284(37), 24948–24957.
(2) Ronen, D., Rosenberg, M. M., Shalev, D. E., Rosenberg, M., Rotem, S., Friedler, A., &
Ravid, S. (2010),
J Biol Chem, 285(10), 7079–7086.
(3) Rosenberg, M. M., Ronen, D., Lahav, N., Nazirov, E., Ravid, S., & Friedler, A. (2013),
J Biol Chem, 288(14), 9779–89.
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