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From Wikipedia, the free encyclopedia

Myosin_head
Scallop myosin in the near-rigor conformation
Identifiers
SymbolMyosin_head
PfamPF00063
Pfam clanCL0023
InterProIPR001609
PROSITEPDOC00017
SCOP21mys / SCOPe / SUPFAM
CDDcd00124
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The myosin head is the part of the thick myofilament made up of myosin that acts in muscle contraction, by sliding over thin myofilaments of actin. Myosin is the major component of the thick filaments and most myosin molecules are composed of a head, neck, and tail domain; the myosin head binds to thin filamentous actin, and uses ATP hydrolysis to generate force and "walk" along the thin filament. Myosin exists as a hexamer of two heavy chains,[1] two alkali light chains, and two regulatory light chains. The heavy chain can be subdivided into the globular head at the N-terminal and the coiled-coil rod-like tail at the C-terminal, although some forms have a globular region in their C-terminal.

There are many cell-specific isoforms of myosin heavy chains, coded for by a multi-gene family.[2] Myosin interacts with actin to convert chemical energy, in the form of ATP, to mechanical energy.[3] The 3-D structure of the head portion of myosin has been determined [4] and a model for actin-myosin complex has been constructed.[5]

The globular head is well conserved,[4][6][7] and is key to contraction. Muscle contraction results from an attachment–detachment cycle between the myosin heads extending from myosin filaments and the sites on actin filaments. The myosin head first attaches to actin together with the products of ATP hydrolysis, performs a power stroke associated with release of hydrolysis products, and detaches from actin upon binding with new ATP. The detached myosin head then hydrolyses ATP, and performs a recovery stroke to restore its initial position. The strokes have been suggested to result from rotation of the lever arm domain around the converter domain, while the catalytic domain remains rigid.[8]

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Transcription

What I want to do in this video is try to understand how two proteins can interact with each other in conjunction with ATP to actually produce mechanical motion. And the reason why I want to do this-- one, it occurs outside of muscle cells as well, but this is really going to be the first video on really how muscles work. And then we'll talk about how nerves actually stimulate muscles to work. So it'll all build up from this video. So what I've done here is I've copy and pasted two images of proteins from Wikipedia. This is myosin. It's actually myosin II because you actually have two strands of the myosin protein. They're interwound around each other so you can see it's this very complex looking protein or enzyme, however you want to talk about it. I'll tell you why it's called an enzyme-- because it actually helps react ATP into ADP and phosphate groups. So that's why it's called an ATPase. It's a subclass of the ATPase enzymes. This right here is actin. What we're going to see in this video is how myosin essentially uses the ATP to essentially crawl along. You can almost view it as an actin rope and that's what creates mechanical energy. So let me draw it. I'll actually draw it on this actin right here. So let's say we have one of these myosin heads. So when I say a myosin head, this is one of the myosin heads right here and then it's connected, it's interwound, it's woven around. This is the other one and it winds around that way. Now let's just say we're just dealing with one of the myosin heads. Let's say it's in this position. Let me see how well I can draw it. Let's say it starts off in a position that looks like that and then this is kind of the tail part that connects to some other structural and we'll talk about that in more detail, but this is my myosin head right there in its starting position, not doing anything. Now, ATP can come along and bond to this myosin head, this enzyme, this protein, this ATPase enzyme. So let me draw some ATP. So ATP comes along and bonds to this guy right here. Let's say that's the-- and it's not going to be this big relative to the protein, but this is just to give you the idea. So soon as the ATP binds to its appropriate site on this enzyme or protein, the enzyme, it detaches from the actin. So let me write this down. So one, ATP binds to myosin head and as soon as that happens, that causes the myosin to release actin. So that's step one. So I start it off with this guy just touching the actin, the ATP comes, and it gets released. So in the next step-- so after that step, it's going to look something like this-- and I want to draw it in the same place. After the next step, it's going to look something like this. It will have released. So now it looks something like that and you have the ATP attached to it still. I know it might be a little bit convoluted when I keep writing over the same thing, but you have the ATP attached to it. Now the next step-- the ATP hydrolizes, the phosphate gets pulled off of it. This is an ATPase enzyme. That's what it does. Let me write that down. And what that does, that releases the energy to cock this myosin protein into kind of a high energy state. So let me do step two. This thing-- it gets hydrolized. It releases energy. We know that ATP is the energy currency of biological systems. So it releases energy. I'm drawing it as a little spark or explosion, but you can really imagine it's changing the confirmation of-- it kind of spring-loads this protein right here to go into a state so it's ready to crawl along the myosin. So in step two-- plus energy, energy and then this-- you can say it cocks the myosin protein or enzyme to high energy. You can imagine it winds the spring, or loads the spring. And confirmation for proteins just mean shape. So step two-- what happens is the phosphate group gets-- they're still attached, but it gets detached from the rest of the ATP. So that becomes ADP and that energy changes the confirmation so that this protein now goes into a position that looks like this. So this is where we end up at the end of step two. Let me make sure I do it right. So at the end of step two, it might look something like this. So the end of step two, the protein looks something like this. This is in its cocked position. It has a lot of energy right now. It's wound up in this position. You still have your ADP. You still have your-- that's your adenosine and let's say you have your two phosphate groups on the ADP and you still have one phosphate group right there. Now, when that phosphate group releases-- so let me write this as step three. Remember, when we started, we were just sitting here. The ATP binds on step one-- actually, it does definitely bind, at the end of step one, that causes the myosin protein to get released. Then after step one, we naturally have step two. The ATP hydrolyzes into ADP phosphate. That releases energy and that allows the myosin protein to get cocked into this high energy position and kind of attach, you can think of it, to the next rung of our actin filament. Now we're in a high energy state. In step three, the phosphate releases. The phosphate is released from myosin in step three. That's step three right there. That's a phosphate group being released. And what this does is, this releases that energy of that cocked position and it causes this myosin protein to push on the actin. This is the power stroke, if you imagine in an engine. This is what's causing the mechanical movement. So when the phosphate group is actually released-- remember, the original release is when you take ATP to ADP in a phosphate. That put it in this spring-loaded position. When the phosphate releases it, this releases the spring. And what that does is it pushes on the actin filament. So you could view this as the power stroke. We're actually creating mechanical energy. So depending on which one you want to view as fixed-- if you view the actin as fixed, whatever myosin is attached to it would move to the left. If you imagine the myosin being fixed, the actin and whatever it's attached to would move to the right, either way. But this is where we fundamentally get the muscle action. And then step four-- you have the ADP released. And then we're exactly where we were before we did step one, except we're just one rung further to the left on the actin molecule. So to me, this is pretty amazing. We actually are seeing how ATP energy can be used to-- we're going from chemical energy or bond energy in ATP to mechanical energy. For me, that's amazing because when I first learned about ATP-- people say, you use ATP to do everything in your cells and contract muscles. Well, gee, how do you go from bond energy to actually contracting things, to actually doing what we see in our everyday world as mechanical energy? And this is really where it all occurs. This is really the core issue that's going on here. And you have to say, well, gee, how this thing change shape and all that? And you have to remember, these proteins, based on what's bonded to it and what's not bonded to it, they change shape. And some of those shapes take more energy to attain, and then if you do the right things, that energy can be released and then it can push another protein. But I find this just fascinating. And now we can build up from this actin and myosin interactions to understand how muscles actually work.

References

  1. ^ Hayashida M, Maita T, Matsuda G (July 1991). "The primary structure of skeletal muscle myosin heavy chain: I. Sequence of the amino-terminal 23 kDa fragment". J. Biochem. 110 (1): 54–9. doi:10.1093/oxfordjournals.jbchem.a123543. PMID 1939027.
  2. ^ Eller M, Stedman HH, Sylvester JE, Fertels SH, Wu QL, Raychowdhury MK, Rubinstein NA, Kelly AM, Sarkar S (October 1989). "Human embryonic myosin heavy chain cDNA. Interspecies sequence conservation of the myosin rod, chromosomal locus and isoform specific transcription of the gene". FEBS Lett. 256 (1–2): 21–8. doi:10.1016/0014-5793(89)81710-7. PMID 2806546. S2CID 12047829.
  3. ^ Warrick HM, De Lozanne A, Leinwand LA, Spudich JA (December 1986). "Conserved protein domains in a myosin heavy chain gene from Dictyostelium discoideum". Proc. Natl. Acad. Sci. U.S.A. 83 (24): 9433–7. Bibcode:1986PNAS...83.9433W. doi:10.1073/pnas.83.24.9433. PMC 387152. PMID 3540939.
  4. ^ a b Rayment I, Rypniewski WR, Schmidt-Bäse K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM (July 1993). "Three-dimensional structure of myosin subfragment-1: a molecular motor". Science. 261 (5117): 50–8. Bibcode:1993Sci...261...50R. doi:10.1126/science.8316857. PMID 8316857.
  5. ^ Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M, Holmes KC, Milligan RA (July 1993). "Structure of the actin-myosin complex and its implications for muscle contraction". Science. 261 (5117): 58–65. Bibcode:1993Sci...261...58R. doi:10.1126/science.8316858. PMID 8316858.
  6. ^ Molloy JE, Burns JE, Kendrick-Jones J, Tregear RT, White DC (November 1995). "Movement and force produced by a single myosin head". Nature. 378 (6553): 209–12. Bibcode:1995Natur.378..209M. doi:10.1038/378209a0. PMID 7477328. S2CID 4334476.
  7. ^ Lewalle A, Steffen W, Stevenson O, Ouyang Z, Sleep J (March 2008). "Single-molecule measurement of the stiffness of the rigor myosin head". Biophysical Journal. 94 (6): 2160–9. Bibcode:2008BpJ....94.2160L. doi:10.1529/biophysj.107.119396. PMC 2257899. PMID 18065470.
  8. ^ Minoda H, Okabe T, Inayoshi Y, Miyakawa T, Miyauchi Y, Tanokura M, Katayama E, Wakabayashi T, Akimoto T, Sugi H (February 2011). "Electron microscopic evidence for the myosin head lever arm mechanism in hydrated myosin filaments using the gas environmental chamber". Biochemical and Biophysical Research Communications. 405 (4): 651–6. doi:10.1016/j.bbrc.2011.01.087. PMID 21281603.
This article incorporates text from the public domain Pfam and InterPro: IPR001609
This page was last edited on 15 October 2023, at 14:47
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