PDBsum entry 5o2l

Motor protein

PDB id: 5o2l

Contents

Protein chain

763 a.a.

Ligands

ADP

BEF

GOL ×8

Metals

_MG

Waters ×239

PDB id:

5o2l

Name:

Motor protein

Title:

Myosin vi motor domain in the pre-transition state

Structure:

Unconventional myosin-vi. Chain: a. Engineered: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Gene: myo6. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.20Å R-factor: 0.184 R-free: 0.227

Authors:

T.Isabet,H.Benisty,A.Houdusse

Key ref:

F.Blanc et al. (2018). An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics. Proc Natl Acad Sci U S A, 115, 6213-6218. PubMed id: 29844196 DOI: 10.1073/pnas.1711512115

Date:

22-May-17 Release date: 23-May-18

Protein chain

Q29122  (MYO6_PIG) -  Unconventional myosin-VI from Sus scrofa

Seq: 1254 a.a.

Struc: 763 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1073/pnas.1711512115

Proc Natl Acad Sci U S A 115:6213-6218 (2018)

PubMed id: 29844196

An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics.

F.Blanc, T.Isabet, H.Benisty, H.L.Sweeney, M.Cecchini, A.Houdusse.

ABSTRACT

Myosins form a class of actin-based, ATPase motor proteins that mediate important cellular functions such as cargo transport and cell motility. Their functional cycle involves two large-scale swings of the lever arm: the force-generating powerstroke, which takes place on actin, and the recovery stroke during which the lever arm is reprimed into an armed configuration. Previous analyses of the prerecovery (postrigor) and postrecovery (prepowerstroke) states predicted that closure of switch II in the ATP binding site precedes the movement of the converter and the lever arm. Here, we report on a crystal structure of myosin VI, called pretransition state (PTS), which was solved at 2.2 Å resolution. Structural analysis and all-atom molecular dynamics simulations are consistent with PTS being an intermediate along the recovery stroke, where the Relay/SH1 elements adopt a postrecovery conformation, and switch II remains open. In this state, the converter appears to be largely uncoupled from the motor domain and explores an ensemble of partially reprimed configurations through extensive, reversible fluctuations. Moreover, we found that the free energy cost of hydrogen-bonding switch II to ATP is lowered by more than 10 kcal/mol compared with the prerecovery state. These results support the conclusion that closing of switch II does not initiate the recovery stroke transition in myosin VI. Rather, they suggest a mechanism in which lever arm repriming would be mostly driven by thermal fluctuations and eventually stabilized by the switch II interaction with the nucleotide in a ratchet-like fashion.