PDBsum entry 6c1h

Structural protein

PDB id: 6c1h

Contents

Protein chains

375 a.a.

729 a.a.

148 a.a.

Ligands

ADP ×5

Metals

_MG ×5

PDB id:

6c1h

Name:

Structural protein

Title:

High-resolution cryo-em structures of actin-bound myosin states reveal the mechanism of myosin force sensing

Structure:

Actin, alpha skeletal muscle. Chain: a, b, c, d, e. Synonym: alpha-actin-1. Unconventional myosin-ib. Chain: p. Synonym: myosin i alpha,mmia,myosin heavy chain myr 1. Calmodulin. Chain: r

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Rattus norvegicus. Rat. Organism_taxid: 10116. Unidentified. Organism_taxid: 32644

Authors:

A.Mentes,A.Huehn,X.Liu,A.Zwolak,R.Dominguez,H.Shuman,E.M.Ostap, C.V.Sindelar

Key ref:

A.Mentes et al. (2018). High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing. Proc Natl Acad Sci U S A, 115, 1292-1297. PubMed id: 29358376

Date:

04-Jan-18 Release date: 31-Jan-18

Protein chains

P68135  (ACTS_RABIT) -  Actin, alpha skeletal muscle from Oryctolagus cuniculus

Seq: 377 a.a.

Struc: 375 a.a.

Protein chain

Q05096  (MYO1B_RAT) -  Unconventional myosin-Ib from Rattus norvegicus

Seq: 1136 a.a.

Struc: 729 a.a.*

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 148 a.a.

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

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E: E.C.3.6.4.- - ?????

Proc Natl Acad Sci U S A 115:1292-1297 (2018)

PubMed id: 29358376

High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing.

A.Mentes, A.Huehn, X.Liu, A.Zwolak, R.Dominguez, H.Shuman, E.M.Ostap, C.V.Sindelar.

ABSTRACT

Myosins adjust their power outputs in response to mechanical loads in an isoform-dependent manner, resulting in their ability to dynamically adapt to a range of motile challenges. Here, we reveal the structural basis for force-sensing based on near-atomic resolution structures of one rigor and two ADP-bound states of myosin-IB (myo1b) bound to actin, determined by cryo-electron microscopy. The two ADP-bound states are separated by a 25° rotation of the lever. The lever of the first ADP state is rotated toward the pointed end of the actin filament and forms a previously unidentified interface with the N-terminal subdomain, which constitutes the upper half of the nucleotide-binding cleft. This pointed-end orientation of the lever blocks ADP release by preventing the N-terminal subdomain from the pivoting required to open the nucleotide binding site, thus revealing how myo1b is inhibited by mechanical loads that restrain lever rotation. The lever of the second ADP state adopts a rigor-like orientation, stabilized by class-specific elements of myo1b. We identify a role for this conformation as an intermediate in the ADP release pathway. Moreover, comparison of our structures with other myosins reveals structural diversity in the actomyosin binding site, and we reveal the high-resolution structure of actin-bound phalloidin, a potent stabilizer of filamentous actin. These results provide a framework to understand the spectrum of force-sensing capacities among the myosin superfamily.