SMART: MYSc domain annotation

MYSc Myosin. Large ATPases.

SMART accession number:	SM00242
Description:	ATPase; molecular motor. Muscle contraction consists of a cyclical interaction between myosin and actin. The core of the myosin structure is similar in fold to that of kinesin.
Interpro abstract (IPR001609):	Muscle contraction is caused by sliding between the thick and thin filaments of the myofibril. Myosin is a major component of thick filaments and exists as a hexamer of 2 heavy chains [(PUBMED:1939027)], 2 alkali light chains, and 2 regulatory light chains. The heavy chain can be subdivided into the N-terminal globular head and the C-terminal coiled-coil rod-like tail, 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 [(PUBMED:2806546)]. Myosin interacts with actin to convert chemical energy, in the form of ATP, to mechanical energy [(PUBMED:3540939)]. The 3-D structure of the head portion of myosin has been determined [(PUBMED:8316857)] and a model for actin-myosin complex has been constructed [(PUBMED:8316858)]. The globular head is well conserved, some highly-conserved regions possibly relating to functional and structural domains [(PUBMED:6576334)]. The rod-like tail starts with an invariant proline residue, and contains many repeats of a 28 residue region, interrupted at 4 regularly-spaced points known as skip residues. Although the sequence of the tail is not well conserved, the chemical character is, hydrophobic, charged and skip residues occuring in a highly ordered and repeated fashion [(PUBMED:6576334)].
GO component:	myosin complex (GO:0016459)
GO function:	motor activity (GO:0003774), ATP binding (GO:0005524)
Family alignment:	View or

There are 3198 MYSc domains in 3196 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a MYSc domain in a specific node, click on it.

This tree shows only several representative species. The complete taxonomic breakdown of all proteins with MYSc domain is also avaliable.

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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Cellular role (predicted cellular role)
Binding / catalysis: ATP-hydrolysis, actin-binding
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Hasson T, Mooseker MS
- The growing family of myosin motors and their role in neurons and sensory cells.
- Curr Opin Neurobiol. 1997; 7: 615-23
- Display abstract
- Biochemical and physiological evidence has suggested that myosins, both conventional and unconventional, are critical for neurosensory activities. In the past few years, this premise has been supported by genetic evidence that has shown that unconventional myosins are essential for the proper functioning of neurons, retina and the sensory cells of the inner ear.
- Cope MJ, Whisstock J, Rayment I, Kendrick-Jones J
- Conservation within the myosin motor domain: implications for structure and function.
- Structure. 1996; 4: 969-87
- Display abstract
- BACKGROUND: Myosins are motors that use energy supplied by ATP to travel along actin filaments. The structure of myosin is known, but the actin-binding site is not well defined, and the mechanisms by which actin activates ATP hydrolysis by myosin, and myosin moves relative to the actin filament, developing force, are not fully understood. Previous phylogenetic analyses of the motor domain of myosins have identified up to twelve classes. We set out to analyse the positions of conserved residues within this domain in detail, and relate the conserved residues to the myosin structure. RESULTS: Our analysis indicates that there are at least thirteen myosin classes. Conserved residues in the motor domain have been positioned within the framework provided by the recent crystal structures, thus helping to define those residues involved in actin and ATP binding, in hydrolysis and in conformational change. This has revealed remarkably poor overall conservation at the site thought to be involved in actin binding, but several highly conserved residues have been identified that may be functionally important. CONCLUSIONS: Information from such a sequence analysis is a useful tool in the further interpretation of X-ray structures. It allows the position of crucial residues from other members of a superfamily to be determined within the framework provided by the known structures and the functional significance of conserved or mutated residues to be assessed.
- Smith CA, Rayment I
- X-ray structure of the magnesium(II).ADP.vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution.
- Biochemistry. 1996; 35: 5404-17
- Display abstract
- The structure of the vanadate-trapped ADP complex of a truncated head of Dictyostelium myosin II consisting of residues Asp 2-Asn 762 has been determined by molecular replacement at 1.9 A resolution and refined to a crystallographic R-factor of 19.4%. The crystals belong to the orthorhombic space group C2221 where a = 84.50 A, b = 145.4 A, and c = 152.8 A. The conformation of the protein is similar to that of MgADP.AlF4.SlDc [Fisher, A.J., et al. (1995) Biochemistry 34, 8960-8972]. The nucleotide binding site contains a complex between MgADP and vanadate where MgADP exhibits a very similar conformation to that seen in previous complexes. The vanadate ion adopts a trigonal bipyramidal coordination. The three equatorial oxygen ligands are fairly short, average 1.7 A, relative to a single bond distance of approximately 1.8 A and are coordinated to the magnesium ion, N zeta of Lys 185, and five other protein ligands. The apical coordination to the vanadate ion is filled by a terminal oxygen on the beta-phosphate of ADP and a water molecule at bond distances of 2.1 and 2.3 A, respectively. The long length of the apical bonds suggests that the bond order is considerably less than unity. This structure confirms the earlier suggestion that vanadate is a model for the transition state of ATP hydrolysis and thus provides insight into those factors that are responsible for catalysis. In particular, it shows that the protein ligands and water structure surrounding the gamma-phosphate pocket are oriented to stabilize a water molecule in an appropriate position for in-line nucleophilic attack on the gamma-phosphorus of ATP. This structure reveals also an orientation of the COOH-terminal region beyond Thr 688 which is very different from that observed in either MgADP.BeFx.SlDc or chicken skeletal myosin subfragment 1. This is consistent with the COOH-terminal region of the molecule playing an important role in the transduction of chemical energy of hydrolysis of ATP into mechanical movement.
- Fisher AJ et al.
- X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-.
- Biochemistry. 1995; 34: 8960-72
- Display abstract
- The three-dimensional structures of the truncated myosin head from Dictyostelium discoideum myosin II complexed with beryllium and aluminum fluoride and magnesium ADP are reported at 2.0 and 2.6 A resolution, respectively. Crystals of the beryllium fluoride-MgADP complex belong to space group P2(1)2(1)2 with unit cell parameters of a = 105.3 A, b = 182.6 A, and c = 54.7 A, whereas the crystals of the aluminum fluoride complex belong to the orthorhombic space group C222(1) with unit cell dimensions of a = 87.9 A, b = 149.0 A, and c = 153.8 A. Chemical modification was not necessary to obtain these crystals. These structures reveal the location of the nucleotide complexes and define the amino acid residues that form the active site. The tertiary structure of the protein complexed with MgADP.BeFx is essentially identical to that observed previously in the three-dimensional model of chicken skeletal muscle myosin subfragment-1 in which no nucleotide was present. By contrast, the complex with MgADP.AlF4- exhibits significant domain movements. The structures suggest that the MgADP.BeFx complex mimics the ATP bound state and the MgADP.AlF4- complex is an analog of the transition state for hydrolysis. The domain movements observed in the MgADP.AlF4- complex indicate that myosin undergoes a conformational change during hydrolysis that is not associated with the nucleotide binding pocket but rather occurs in the COOH-terminal segment of the myosin motor domain.
- Smith CA, Rayment I
- X-ray structure of the magnesium(II)-pyrophosphate complex of the truncated head of Dictyostelium discoideum myosin to 2.7 A resolution.
- Biochemistry. 1995; 34: 8973-81
- Display abstract
- The structure of the magnesium pyrophosphate complex of the truncated head of Dictyostelium myosin has been determined by molecular replacement at 2.7 A resolution and refined to a crystallographic R-factor of 16.0%. The crystals belong to the orthorhombic space group P2(1)2(1)2, where a = 105.2 A, b = 182.1 A, and c = 54.5 A. The conformation of the protein around the magnesium pyrophosphate is very similar to that seen when magnesium ADP-beryllium fluoride binds in the active site. The latter complex mimics the binding of ATP prior to hydrolysis. The pyrophosphate molecule occupies the beta- and gamma-phosphate sites, where the two phosphorus atoms are in the same positions as the beta-phosphate and the BeFx moiety of the beryllium fluoride-trapped ADP. The surrounding active site residues are almost perfectly superimposable in the two structures and the hydrogen-bonding interactions that the PPi makes with the protein are essentially identical. The similarity between the MgPPi and MgADP.BeFx complex with S1Dc suggests that the conformational change, which occurs when ATP binds to actomyosin and which reduces the affinity of myosin for actin, is caused by the binding of the gamma- and beta-phosphate groups of the nucleotide. This then implies that the role of the remainder of the substrate is to increase the binding affinity for myosin and thus to drive the equilibrium toward dissociation of myosin from actin.
- Rayment I, Holden HM
- The three-dimensional structure of a molecular motor.
- Trends Biochem Sci. 1994; 19: 129-34
- Display abstract
- Myosin is one of only three proteins known to convert chemical energy into mechanical work. Although the chemical, kinetic and physiological characteristics of this protein have been studied extensively, it has been difficult to define its molecular basis of movement. With the recent X-ray structural determination of the myosin head, however, it is now possible to put forward a hypothesis on how myosin might function as a molecular motor.
- Xie X et al.
- Structure of the regulatory domain of scallop myosin at 2.8 A resolution.
- Nature. 1994; 368: 306-12
- Display abstract
- The regulatory domain of scallop myosin is a three-chain protein complex that switches on this motor in response to Ca2+ binding. This domain has been crystallized and the structure solved to 2.8 A resolution. Side-chain interactions link the two light chains in tandem to adjacent segments of the heavy chain bearing the IQ-sequence motif. The Ca(2+)-binding site is a novel EF-hand motif on the essential light chain and is stabilized by linkages involving the heavy chain and both light chains, accounting for the requirement of all three chains for Ca2+ binding and regulation in the intact myosin molecule.
- Rayment I et al.
- Three-dimensional structure of myosin subfragment-1: a molecular motor.
- Science. 1993; 261: 50-8
- Display abstract
- Directed movement is a characteristic of many living organisms and occurs as a result of the transformation of chemical energy into mechanical energy. Myosin is one of three families of molecular motors that are responsible for cellular motility. The three-dimensional structure of the head portion of myosin, or subfragment-1, which contains both the actin and nucleotide binding sites, is described. This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility.
- Rayment I et al.
- Structure of the actin-myosin complex and its implications for muscle contraction.
- Science. 1993; 261: 58-65
- Display abstract
- Muscle contraction consists of a cyclical interaction between myosin and actin driven by the concomitant hydrolysis of adenosine triphosphate (ATP). A model for the rigor complex of F actin and the myosin head was obtained by combining the molecular structures of the individual proteins with the low-resolution electron density maps of the complex derived by cryo-electron microscopy and image analysis. The spatial relation between the ATP binding pocket on myosin and the major contact area on actin suggests a working hypothesis for the crossbridge cycle that is consistent with previous independent structural and biochemical studies.
Disease (disease genes where sequence variants are found in this domain)

Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Protein	Disease
Myosin-9 (P35579) (SMART)	OMIM:155100: May-Hegglin anomaly OMIM:160775: May-Hegglin anomaly OMIM:155100: Fechtner syndrome OMIM:153640: Sebastian syndrome OMIM:605249: Deafness, autosomal dominant 17 OMIM:603622:
UNKNOWN (SMART)	OMIM:160760: Cardiomyopathy, familial hypertrophic, 1 OMIM:192600: ?Central core disease, one form
Myosin-VIIa (Q13402) (SMART)	OMIM:276903: Usher syndrome, type 1B ; Deafness, autosomal recessive 2, neurosensory OMIM:600060: Deafness, autosomal dominant 11, neurosensory OMIM:601317:

3D Structures of MYSc domains in PDB

PDB code	Main view	Title
1b7t		Myosin digested by papain
1br1		Smooth muscle myosin motor domain-essential light chain complex with mgadp.alf4 bound at the active site
1br2		Smooth muscle myosin motor domain complexed with mgadp.alf4
1br4		Smooth muscle myosin motor domain-essential light chain complex with mgadp.bef3 bound at the active site
1d0x		Dictyostelium myosin s1dc (motor domain fragment) complexed with m-nitrophenyl aminoethyldiphosphate beryllium trifluoride.
1d0y		Dictyostelium myosin s1dc (motor domain fragment) complexed with o-nitrophenyl aminoethyldiphosphate beryllium fluoride.
1d0z		Dictyostelium myosin s1dc (motor domain fragment) complexed with p-nitrophenyl aminoethyldiphosphate beryllium trifluoride.
1d1a		Dictyostelium myosin s1dc (motor domain fragment) complexed with o,p-dinitrophenyl aminoethyldiphosphate beryllium trifluoride.
1d1b		Dictyostelium myosin s1dc (motor domain fragment) complexed with o,p-dinitrophenyl aminopropyldiphosphate beryllium trifluoride.
1d1c		Dictyostelium myosin s1dc (motor domain fragment) complexed with n-methyl-o-nitrophenyl aminoethyldiphosphate beryllium trifluoride.
1dfk		Nucleotide-free scallop myosin s1-near rigor state
1dfl		Scallop myosin s1 complexed with mgadp:vanadate-transition state
1fmv		Crystal structure of the apo motor domain of dictyostellium myosin ii
1fmw		Crystal structure of the mgatp complex for the motor domain of dictyostelium myosin ii
1g8x		Structure of a genetically engineered molecular motor
1i84		Cryo-em structure of the heavy meromyosin subfragment of chicken gizzard smooth muscle myosin with regulatory light chain in the dephosphorylated state. only c alphas provided for regulatory light chain. only backbone atoms provided for s2 fragment.
1jwy		Crystal structure of the dynamin a gtpase domain complexed with gdp, determined as myosin fusion
1jx2		Crystal structure of the nucleotide-free dynamin a gtpase domain, determined as myosin fusion
1kk7		Scallop myosin in the near rigor conformation
1kk8		Scallop myosin (s1-adp-befx) in the actin-detached conformation
1kqm		Scallop myosin s1-amppnp in the actin-detached conformation
1kwo		Scallop myosin s1-atpgammas-p-pdm in the actin-detached conformation
1l2o		Scallop myosin s1-adp-p-pdm in the actin-detached conformation
1lkx		Motor domain of myoe, a class-i myosin
1lvk		X-ray crystal structure of the mg (dot) 2'(3')-o-(n- methylanthraniloyl) nucleotide bound to dictyostelium discoideum myosin motor domain
1m8q		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1mma		X-ray structures of the mgadp, mgatpgammas, and mgamppnp complexes of the dictyostelium discoideum myosin motor domain
1mmd		Truncated head of myosin from dictyostelium discoideum complexed with mgadp-bef3
1mmg		X-ray structures of the mgadp, mgatpgammas, and mgamppnp complexes of the dictyostelium discoideum myosin motor domain
1mmn		X-ray structures of the mgadp, mgatpgammas, and mgamppnp complexes of the dictyostelium discoideum myosin motor domain
1mnd		Truncated head of myosin from dictyostelium discoideum complexed with mgadp-alf4
1mne		Truncated head of myosin from dictyostelium discoideum complexed with mg-pyrophosphate
1mvw		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o18		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o19		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1a		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1b		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1c		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1d		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1e		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1f		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1g		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1oe9		Crystal structure of myosin v motor with essential light chain - nucleotide-free
1qvi		Crystal structure of scallop myosin s1 in the pre-power stroke state to 2.6 angstrom resolution: flexibility and function in the head
1s5g		Structure of scallop myosin s1 reveals a novel nucleotide conformation
1sr6		Structure of nucleotide-free scallop myosin s1
1vom		Complex between dictyostelium myosin and mgadp and vanadate at 1.9a resolution
1w7i		Crystal structure of myosin v motor without nucleotide soaked in 10 mm mgadp
1w7j		Crystal structure of myosin v motor with essential light chain + adp-befx - near rigor
1w8j		Crystal structure of myosin v motor domain - nucleotide-free
1w9i		Myosin ii dictyostelium discoideum motor domain s456y bound with mgadp-befx
1w9j		Myosin ii dictyostelium discoideum motor domain s456y bound with mgadp-alf4
1w9k		Dictyostelium discoideum myosin ii motor domain s456e with bound mgadp-befx
1w9l		Myosin ii dictyostelium discoideum motor domain s456e bound with mgadp-alf4
1yv3		The structural basis of blebbistatin inhibition and specificity for myosin ii
2aka		Structure of the nucleotide-free myosin ii motor domain from dictyostelium discoideum fused to the gtpase domain of dynamin 1 from rattus norvegicus
2bkh		Myosin vi nucleotide-free (mdinsert2) crystal structure
2bki		Myosin vi nucleotide-free (mdinsert2-iq) crystal structure
2dfs		3-d structure of myosin-v inhibited state
2ec6		Placopecten striated muscle myosin ii
2ekv		The crystal structure of rigor like squid myosin s1 in the absence of nucleotide
2ekw		The crystal structure of squid myosin s1 in the presence of so4 2-
2jhr		Crystal structure of myosin-2 motor domain in complex with adp-metavanadate and pentabromopseudilin
2jj9		Crystal structure of myosin-2 in complex with adp- metavanadate
2mys		Myosin subfragment-1, alpha carbon coordinates only for the two light chains
2os8		Rigor-like structures of muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor
2otg		Rigor-like structures of muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor
2ovk		Crystal structure of rigor-like squid myosin s1
2oy6		Crystal structure of squid mg.adp myosin s1
2v26		Myosin vi (md) pre-powerstroke state (mg.adp.vo4)
2vas		Myosin vi (md-insert2-cam, delta-insert1) post-rigor state
2vb6		Myosin vi (md-insert2-cam, delta insert1) post-rigor state ( crystal form 2)
3bz7		Crystal structures of (s)-(-)-blebbistatin analogs bound to dictyostelium discoideum myosin ii
3bz8		Crystal structures of (s)-(-)-blebbistatin analogs bound to dictyostelium discoideum myosin ii
3bz9		Crystal structures of (s)-(-)-blebbistatin analogs bound to dictyostelium discoideum myosin ii
3dtp		Tarantula heavy meromyosin obtained by flexible docking to tarantula muscle thick filament cryo-em 3d-map
3i5f		Crystal structure of squid mg.adp myosin s1
3i5g		Crystal structure of rigor-like squid myosin s1
3i5h		The crystal structure of rigor like squid myosin s1 in the absence of nucleotide
3i5i		The crystal structure of squid myosin s1 in the presence of so4 2-

Links (links to other resources describing this domain)
PFAM myosin_head
INTERPRO IPR001609

PFAM	myosin_head
INTERPRO	IPR001609