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TitleCryo-EM structures reveal specialization at the myosin VI-actin interface and a mechanism of force sensitivity.
Journal, issue, pagesElife, Vol. 6, Year 2017
Publish dateDec 4, 2017
AuthorsPinar S Gurel / Laura Y Kim / Paul V Ruijgrok / Tosan Omabegho / Zev Bryant / Gregory M Alushin /
PubMed AbstractDespite extensive scrutiny of the myosin superfamily, the lack of high-resolution structures of actin-bound states has prevented a complete description of its mechanochemical cycle and limited ...Despite extensive scrutiny of the myosin superfamily, the lack of high-resolution structures of actin-bound states has prevented a complete description of its mechanochemical cycle and limited insight into how sequence and structural diversification of the motor domain gives rise to specialized functional properties. Here we present cryo-EM structures of the unique minus-end directed myosin VI motor domain in rigor (4.6 Å) and Mg-ADP (5.5 Å) states bound to F-actin. Comparison to the myosin IIC-F-actin rigor complex reveals an almost complete lack of conservation of residues at the actin-myosin interface despite preservation of the primary sequence regions composing it, suggesting an evolutionary path for motor specialization. Additionally, analysis of the transition from ADP to rigor provides a structural rationale for force sensitivity in this step of the mechanochemical cycle. Finally, we observe reciprocal rearrangements in actin and myosin accompanying the transition between these states, supporting a role for actin structural plasticity during force generation by myosin VI.
External linksElife / PubMed:29199952 / PubMed Central
MethodsEM (helical sym.)
Resolution4.6 - 7.5 Å
Structure data

EMDB-7115, PDB-6bno:
Structure of bare actin filament
PDB-6bnu: Structure of bare actin filament, backbone-averaged with sidechains truncated to alanine
Method: EM (helical sym.) / Resolution: 5.5 Å

EMDB-7116, PDB-6bnp:
CryoEM structure of MyosinVI-actin complex in the rigor (nucleotide-free) state
PDB-6bnv: CryoEM structure of MyosinVI-actin complex in the rigor (nucleotide-free) state, backbone-averaged with side chains truncated to alanine
Method: EM (helical sym.) / Resolution: 4.6 Å

EMDB-7117, PDB-6bnq:
CryoEM structure of Myosin VI-Actin complex in the ADP state
PDB-6bnw: CryoEM structure of Myosin VI-Actin complex in the ADP state, backbone-averaged with side chains truncated to alanine
Method: EM (helical sym.) / Resolution: 5.5 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • oryctolagus cuniculus (rabbit)
  • sus scrofa (pig)
  • gallus gallus (chicken)
KeywordsCONTRACTILE PROTEIN / Cytoskeleton / Filament / complex

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