English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Crystal structures of human cardiac β-myosin II S2-Δ provide insight into the functional role of the S2 subfragment

Blankenfeldt, W., Thomä, N. H., Wray, J., Gautel, M., & Schlichting, I. (2006). Crystal structures of human cardiac β-myosin II S2-Δ provide insight into the functional role of the S2 subfragment. Proceedings of the National Academy of Sciences of the United States of America, 103(47), 17713-17717. doi:10.1073/pnas.0606741103.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-3C75-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-3C77-1
Genre: Journal Article
Other : Crystal structures of human cardiac beta-myosin II S2-{Delta} provide insight into the functional role of the S2 subfragment

Files

show Files
hide Files
:
PNAS_103_2006_17713.pdf (Any fulltext), 2MB
 
File Permalink:
-
Name:
PNAS_103_2006_17713.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Medical Research, Heidelberg; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Creators

show
hide
 Creators:
Blankenfeldt, Wulf, Author
Thomä, Nicolas H., Author
Wray, John1, 2, Author              
Gautel, Mathias, Author
Schlichting, Ilme1, 2, Author              
Affiliations:
1Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society, ou_1497700              
2Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497712              

Content

show
hide
Free keywords: coiled coil; muscle; crystallography; regulation; familial hypertrophic cardiomyopathy
 Abstract: Myosin II is the major component of the muscle thick filament. It consists of two N-terminal S1 subfragments ("heads") connected to a long dimeric coiled-coil rod. The rod is in itself twofold symmetric, but in the filament, the two heads point away from the filament surface and are therefore not equivalent. This breaking of symmetry requires the initial section of the rod, subfragment 2 (S2), to be relatively flexible. S2 is an important functional element, involved in various mechanisms by which the activity of smooth and striated muscle is regulated. We have determined crystal structures of the 126 N-terminal residues of S2 from human cardiac beta-myosin II (S2-Delta), of both WT and the disease-associated E924K mutant. S2-Delta is a straight parallel dimeric coiled coil, but the N terminus of one chain is disordered in WT-S2-Delta due to crystal contacts, indicative of unstable local structure. Bulky noncanonical side chains pack into a/d positions of S2-Delta's N terminus, leading to defined local asymmetry and axial stagger, which could induce nonequivalence of the S1 subfragments. Additionally, S2 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Delta, the first of which may provide a binding interface for the "blocked head" of smooth muscle myosin in the OFF state. The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C.

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: National Academy of Sciences
Pages: - Volume / Issue: 103 (47) Sequence Number: - Start / End Page: 17713 - 17717 Identifier: ISSN: 0027-8424
CoNE: /journals/resource/954925427230