Myosin
Myosin is one of three major classes of molecular motor proteins: myosin, dynein, and kinesin. As the most abundant of these proteins myosin plays a structural and enzymatic role in muscle contraction and intracellular motility. Myosin was first discovered in muscle in the 19th century. [1] Myosin is a superfamily of proteins which bind actin, hydrolyze ATP and transduce force. Thus most are located in muscle cells. Composed of head, neck and tail domains. Head domain binds the actin and moves along it. The neck is a linker and binds the light chains which have a regulatory function. The tail interacts with cargo molecules (CBD)m. There are 18 classes of myosin. Myosin II (MII) is best studied and contains 2 heavy chains (HC) which constitute the head and tail domains and 4 light chains (LC) which are referred to as the essential LC (ELC) and the regulatory LC (RLC). The images at the left and at the right correspond to one representative Myosin, i.e. the crystal structure of from Myosin Gallus gallus (2mys).
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| Chicken myosin with di-methylated lysines complex with sulfate and Mg+2 ion 2mys | |||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystallization and X-ray diffractionCrystallization and X-ray diffraction
Myosin is found in abundance, therefore it can be prepared in gram quantities. [2] For nearly 30 years the myosin head was resistant to crystallization, yet by 1993 researchers discovered a mechanism to obtain x-ray quality crystals. The process modified the protein by reductive methylation. X-ray data was used to determine the tertiary structure of the protein. [2]
StructureStructure
Myosin has a molecular size of approximately 520 kilodaltons with a total of six subunits. It has two 220 kD heavy chains which make the majority of the overall structure and two pairs of light chains which vary in size.[2] The molecule is asymmetric, having a long tail and two globular heads. Each heavy chains composes the bulk of one of the globular heads. Subfragment-1(S1) also termed the myosin head consists of ATP, actin, and two light chain binding sites. Each globular head has a heavy chain and two light chains for a combined molecular size of about 130 kD. [2]
The myosin head is assymetrical with a length of 165 Angstroms and 65 Angstroms in width, with a total thickness of about 40 Angstroms. [2] About 48% of the amino acid residues in the myosin head are dominated by α helices. At the carboxyl terminus one long α helix of about 85 Angstroms extends in a left-handed coil. This particular helix forms the light chain binding region of the globular domain [2] The amino terminus of each heavy chain has a large globular domain containing the site of ATP hydrolysis.
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FunctionFunction
Molecules of myosin aggregate in muscle cells to form thick filaments. [3] The rodlike structure of these thick filaments act as the core in the muscle contractile unit. The aggregation of several hundred myosin forms a bipolar structure which stacks in regular arrays. Muscles consist of another protein called actin. Actin forms the thin filament in muscle fibers. Myosin and actin interact through weak bonds. Without ATP bound, the myosin head binds tightly to actin. With ATP bound, myosin releases the actin subunit and interacts with another subunit further down the thin filament. This process continues in cycle, producing movement. Interaction of myosin and actin is regulated by two other proteins, tropomyosin and troponin. [3]
The cycle of myosin-actin interaction is outlined as follows: [3]
1. ATP binds to myosin and a binding site opens on myosin head to disrupt the actin-myosin interaction, actin is released. ATP is hydrolyzed
2. a conformational change moving the protein to a "high-energy" state causes the myosin head to change orientation moving it to bind with the actin subunit closer the a region called the Z disk than the previous actin subunit
3. the binding site is closed, strengthening the myosin-actin binding
4. a quickly follows and the myosin head undergoes an additional conformational change bringing it back to the resting state in which it began
Click the link to access DNAtube video "A Moving Myosin Motor Protein" http://www.dnatube.com/video/389/A-Moving-Myosin-Motor-Protein-myosin-actin-interaction
3D Structures of Myosin3D Structures of Myosin
Update June 2011
Myosin IMyosin I
1lkx – DdMI HC - Dictyostelium discoideum
2drk, 2drm – MI HC + 10-mer peptide – Acanthamoeba castellanii
Myosin IIMyosin II
1o1g, 1o1a , 1o1b, 1o1c, 1o1d, 1o1e, 1o1f, 1o18, 1o19, 1mvw, 1m8q – cMII RLC+ELC+HC+actin – tomography - chicken
3lla – cMII HC alpha-kinase domain+AMPPCP
3lmh – cMII HC alpha-kinase domain+ADP
3lmi – cMII HC alpha-kinase domain (mutant) +ATP
2fxm, 2fxo – hMII HC S2 fragment - human
3i5f – LpMII RLC+HC+ADP+Mg – Loligo pealei
3i5g, 3i5h – LpMII RLC+HC+ELC
3i5i – LpMII RLC+HC+ELC+SO4
2jhr – DdMII HC+ADP-VO4+pentabromopseudilin
2xo8 - DdMII HC motor domain +pseudilin derivative
3bz7, 3bz9, 1iv3, 3bz8 - DdMII HC+blebbistatin
3mjx - DdMII HC+blebbistatin + ADP-VO4
3mnq - DdMII HC motor domain + ADP-VO4 + reservatrol
3bas, 3bat, 1fmv - DdMII HC
1fmw – DdMII HC+ATP
1jwy, 1jx2 – DdMII HC+dynamin-1
1d0x, 1d0y, 1d0z, 1d1a, 1d1b, 1d1c – DdMII HC (mutant)+BeF3 derivative
1g8x – DdMII+actinin 3
2jj9, 2x9h - DdMII HC+ADP-VO4
3mkd - DdMII HC motor domain (mutant) + ADP-VO4
1lvk, 1mma, 1mmg, 1mmn – DdMII HC (mutant)+Mg+nucleotide
1myh, 1myk, 1myl, 3myh, 3myl - DdMII HC (mutant)
1mne - DdMII HC (mutant)+Mg+pyrophosphate
1vom - DdMII HC (truncated)+Mg+ADP-VO4
1mmd, 1w9i, 1w9k - DdMII HC (mutant)+Mg+ADP+BeF3
1mnd, 1w9j, 1w9l - DdMII HC (mutant)+Mg+ADP+AlF4
2aka - DdMII HC+dynamin-1
1n2d – ScMII LC+IQ2 IQ3 motifs from Myo2p
1m45 - ScMII LC+IQ2 motif from Myo2p
1m46 - ScMII LC+IQ4 motif from Myo2p
2bl0 – MII RLC +RHC – Physarum polycephalum
Myosin IIIMyosin III
2btt – ScMIII SH3 domain – NMR
1ruw, 1va7 – yMIII SH3 domain
Myosin IVMyosin IV
3mmi – yMIV globular tail
Myosin VMyosin V
1w7i – cMV HC+LC+Mg+ADP
1w7j - cMV HC+LC+BEFX+ADP
1w8j – cMV HC
1oe9 – cMV HC+LC
1br2 – cMV HC+Mg+ADP+AlF4
2fcd – ScMV LC N-terminal – Saccharomices cerevisiae – NMR
2fce – ScMV LC C-terminal – NMR
2f6h – ScMV CBD
1yp5 – yMV SH3 domain
2ix7 – mMV+apo-calmodulin - mouse
Myosin VIMyosin VI
2kia – mMVI CBD – mouse – NMR
3h8d - mMVI CBD+Dab2 peptide
3gn4, 2vb6 - pMVI neck+calmodulin – pig
2vas, 3l9i - pMVI neck (mutant)+calmodulin
2v26 - pMVI neck+Mg+ADP-VO4
2bkh, 2bki – pMVI HC+calmodulin
2x51 - pMVI d insert1 + calmodulin
Myosin VIIMyosin VII
2i0n - DdMVII SH3 domain - NMR
3pvl - mMVII SH3 domain+hUsher syndrome type 1G protein
Myosin XMyosin X
3pzd - hMX myth4-ferm tandem + netrin receptor DCC
Flight muscle myosinFlight muscle myosin
1i84, 2w4a, 2w4g, 2w4h - cRLC+cELC+cHC – cryoEM
2mys - cRLC+cELC+cHC - papain digested
1lkm – cHC alpha-kinase domain+AMP
2dfs – cHC+calmodulin
1br4 – cELC+cHC+Mg+ADP+BeF3
1br1 – cELC+Mg+ADP+AlF4
2xrf – hLC
3jtd, 2w4t, 2w4v, 2w4w, 1scm – AiRLC+AiELC+AiHC - Argopecten irradians
1b7t - AiRLC+AiELC+AiHC papain digested
3jvt - sRLC+sELC+sHC+Ca – Scallop
2ec6, 2os8, 2otg, 1s5g, 1sr6, 1qvi, 1kk7, 1dfk, 3pn7 - sRLC+sELC+sHC
1kqm - sRLC+sELC+sHC+AMPPNP
1kwo - sRLC+sELC+sHC+ATPgS-PDM
1l2o - sRLC+sELC+sHC+ADP-PDM
1kk8 - sRLC+sELC+sHC+ADP-BEFX
1dfl - sRLC+sELC+sHC+ADP-VO4+Mg
1wdc - sRLC+sELC+sHC - digested
3dtp - RLC+HC+ELC – tarantula – Cryo EM
Literature CitedLiterature Cited
- ↑ Spudich JA, Finer J, Simmons B, Ruppel K, Patterson B, Uyeda T. Myosin structure and function. Cold Spring Harb Symp Quant Biol. 1995;60:783-91. PMID:8824453
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Rayment I, Rypniewski WR, Schmidt-Base K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science. 1993 Jul 2;261(5117):50-8. PMID:8316857
- ↑ 3.0 3.1 3.2 Nelson, D. and Cox, M.(2005). Lehninger Principles of Biochemistry. 4th ed. p.1119.