The document categorizes and describes the main proteins found in muscle fibers. It discusses myofibril proteins that make up the contractile apparatus, such as actin and myosin. It also describes the dystrophin-glycoprotein complex that links the intracellular cytoskeleton to the extracellular matrix. This complex includes dystrophin, dystroglycan, sarcoglycans, and other proteins. The document further discusses nuclear envelope proteins and categorizes the various muscle proteins based on their location in the muscle cell.

1. MUSCLE PROTEINS
BY- AMIT SHANKAR SINGH

2. INTRODUCTION
• The myofiber is the functional unit of skeletal muscle and is a multinucleated
tubular structure formed from the fusion of multiple mono-nucleated muscle
cells (myoblasts).
• In addition to typical cellular organelles, the cytoplasm (sarcoplasm) of a myofiber
contains a regular array of contractile units (sarcomeres) comprised of actin-
containing thin filaments and myosin-containing thick filaments that, along with
additional structural and regulatory proteins, are arranged longitudinally as
myofibrils.

3. • The peripheral myofibrils are connected to the sarcolemma along the Z-disks
via interactions with sub-sarcolemmal protein complexes.
• These structures transmit contractile forces from sarcomeres of one myofiber
to another, which prevents sarcolemma ruptures by synchronizing contraction
of myofibers within a muscle. Sarcolemma is firmly attached to the basal
lamina, With another set of Extracellular matrix proteins providing stability.

4. CATEGORISATION OF MUSCLE
PROTIENS
• MUSCLE PROTIENS CAN BE CATEGORISED ACCORDING TO THERE
LOCATION IN MYOBLASTS-
• MYOFIBRIL PROTEINS- Main contractile protiens
• DYSTROPHIN-GLYCOPROTEIN COMPLEX-CONSTITUTED BY
 SARCOLEMMAL PROTEINS-
1. EXTRACELLULAR MATRIX PROTEINS
2. TRANSMEMBRANE PROTEINS
3. INTRACELLULAR PROTEINS
 CYTOSKELETAL PROTEINS
• NUCLEAR ENVELOPE PROTIENS

5. CATEGORISATION OF MUSCLE PROTIENS
MYOFIBRIL
PROTEINS
DYSTROPHIN-
GLYCOPROTEI
N COMPLEX
NUCLEAR
ENVELOPE
PROTIENS

6. MYOFIBRIL PROTEINS

7. MYOSIN

8. ACTIN

9. MUSCLE PROTEINS IN MYOFIBRILS
LOCATION PROTIEN
Filaments Actin
Myosin
Troponin I, C, and T Subunits
Tropomyosin
Z disk α-actinin
Desmin
Vimentin
Nebulin
Titin
M line Paramyosin
C-protein
M-protein

10. Z BAND PROTIENS

11. Dystrophin-glycoprotein complex (DGC)
• DGC represents a link between the extracellular matrix and the cytoskeleton and
it is crucial for the structural stability of the plasma membrane.
• DGC is a group of peripheral and integral membrane proteins which forms a
mechanical linkage between the F-actin cytoskeleton and the extracellular matrix.
The DGC in skeletal muscle is
formed by-
1. Cytosolic dystrophin,
syntrophins and
dystrobrevins;
2. Heavily glycosylated
dystroglycan-complex, formed
by two subunits, α- and β-
Dystroglycan.
3. Four sarcoglycans, α, β, γ
and δ, plus sarcospan,
syntrophins (α-1, β-1 and β-2)
and dystrobrevins.

12. DYSTROPHIN-GLYCOPROTEIN COMPLEX

13. Dystroglycan
• Dystroglycan represents a link between the extracellular matrix and the
cytoskeleton and it is crucial for the structural stability of the plasma
membrane.
• Dystroglycan is composed of two subunits, α- and β- Dystroglycan. Alpha-
Dystroglycan binds to a number of extracellular matrix molecules,
laminin, agrin and perlecan and it interacts tightly with β- Dystroglycan.
The cytoplasmic tail of β- Dystroglycan binds dystrophin, caveolin-3 and other
cytoplasmic proteins involved in signal trasduction.

14. α- and β- Dystroglycan

15. DYSTROPHIN
• Dystrophin is an intracellular, rod-shaped protein with four major
functional domains. This protein is localized to the inner surface of the
sarcolemma, with a high abundance at Z-disc.
• The N terminal and a portion of the middle rod domain interact with the
cytoskeletal filamentous actin (F-actin) which interacts with Z-disc,
whereas the C-terminal domain interacts with the cytodomain of
transmembraneous β-Dystroglycan along with dystrobrevin and
syntrophin protiens of DGC.

16. DYSTROPHIN
• The extracellular domain of β-Dystroglycan binds to
the peripheral membrane protein α-Dystroglycan that
interacts with several components of the basement
membrane of the skeletal muscle, laminin, perlecan
and agrin.
• Therefore through an extensive network of interacting
proteins Dystrophin physically couple the sarcolemma
with the Z disk of force-generating myofibrils.
• The absence of dystrophin in humans leads to skeletal
musle disorganization, sarcolemmal fragility, muscle
weakness and necrosis.

17. Sarcoglycans
• Five transmembrane proteins, all expressed primarily in skeletal muscle,
constitute the sarcoglycan family: α (50 kDa, also called adhalin), β (43 kDa), γ
(35 kDa), δ (35 kDa) and ε (50 kDa).
• Dystrophin and γ sarcoglycan can interact directly, and δ sarcoglycan appears
to be coordinated to the dystroglycan complex.
• Mutations abolishing the expression of any one of the sarcoglycans cause loss
of the others from the sarcolemma; the four recessive limb girdle muscular
dystrophies 2D, 2E, 2C and 2F are caused by absence of the α, β, γ or δ
sarcoglycans, respectively

18. Desmin
• Desmin connects Z-disks of neighboring
myofibrils and anchors myofibrils to intracellular
organelles, such as mitochondria and the
nucleus, and to the sarcolemma, to maintain a
spatial organization between myofibrils and
other structural components of the myofiber.
• Mutations in desmin are associated with the
autosomal dominant LGMD1D with dilated
cardiomyopathy, with characteristic desmin-
positive protein aggregates within the
sarcoplasma.

19. Caveolin 3
• T-tubules are essential for the coordinated contraction of muscle
fibers. Their composition is similar to that of caveolae, which are
plasma membrane invaginations 50–100nm in diameter with the
biochemical properties of lipid rafts.
• Caveolin 3 is a muscle-specific isoform of caveolin that associates
with developing T-tubules and has been credited with several
additional roles in muscle, including inhibition of nNOS at the cell
surface.
• Caveolins are small membrane-based molecules that span the
membrane twice in a hairpin fashion without a significant
extracellular domain.
• Caveolin 3 is partly associated with the DGC by binding to the
intracellular domain of beta-dystroglycan.
• However, most caveolin 3 appears not to be directly associated
with the complex.

20. Dystrobrevins and syntrophins
• The dystrobrevins and syntrophins are structurally related
to dystrophin's C-terminus, with which they also are
associated, thus they are at the same time dystrophin-
related and dystrophin-associated proteins.
• Among other interactions, dystrobrevin also appears to
bind the intracellular portion of the sarcoglycan complex,
thus establishing a link between dystrophin and
sarcoglycan. The novel proteins syncoilin and desmuslin
bind to dystrobrevin and also to the intermediate filament
desmin, thus providing a link to the muscle intermediate
filament cytoskeleton.
• Dystrobrevin likely acts with syntrophins to recruit signaling
proteins to the DGC (nNOS: nitric oxide synthase)

21. Sarcospan
• Sarcospan is a 25 kDa membrane protein with
four transmembrane domains and intracellular N-
and C-termini, a unique feature for
transmembrane proteins of the DAPC.
• Expression is seen predominantly in skeletal and
cardiac muscle, but shorter isoforms exist in
other tissues.
• No human disease is currently known to be
• associated with sarcospan deficiency.

22. Syncoilin
• Syncoilin was first identified via its interaction with α-
dystrobrevin in muscle.
• Sequence analysis revealed the presence of a unique N-
terminus domain and a coiledcoil domain that is typical of
those found in intermediate filament proteins.
• Syncoilin is highly expressed in skeletal, cardiac and smooth
muscle at the sarcolemma, Z-lines and neuromuscular
junction.
• Through its interaction with desmin, syncoilin is thought to
provide a link between the DGC at the sarcolemma and the
intermediate filament protein network

23. Nitric Oxide Synthetase
• The production of nitric oxide (NO) by nNOS is
important for increasing local blood flow to
match the increased metabolic load of
contracting muscles, such as during exercise.
• The presence of nNOS at the sarcolemma is
mediated through syntrophin, and it is lost in
a number of muscular dystrophies including
DMD.

24. Laminin-2 (Merosin)
• Laminin-2 is composed of α2, β1 and γ1 chains
and binds to α-dystroglycan and the α7β1
integrin complex.
• Laminins are thought to form the structural part
of the basement membranes along with collagen
IV, nidogen and perlecan.
• Mutations of the laminin α2 gene cause severe
congenital muscular dystrophy but do not appear
to cause damage to the sarcolemma

25. Dysferlin
• Dysferlin has a membrane-spanning domain,
but in contrast to the sarcoglycans, its major
proportion is contained within the cell.
• It contains multiple C2 domains, which are
thought to play a role in calcium mediated
membrane fusion events.
• Thus, a role for dysferlin in membrane
maintenance and repair has been suggested.

26. Collagen type VI
• Collagen type VI is unique among the
collagens in that it forms beaded microfibrils
that can be found in most extracellular
matrices.
• Collagen type VI seems to be in intimate
contact with basement membranes through
interactions with collagen type IV.
• It also directly binds to cell surface receptors.

27. MUSCULAR DYSTROPHIES CAUSED BY DEFECT IN MUSCLE
PROTIENS

29. Costameres
• The contractile proteins of myofibers are anchored in Z
disks, which are connected to the sarcolemma and the ECM
via costameres.
• Costameres are the periodic membrane-associated bands
that are rich in vinculin and juxtaposed to the Z-line and M-
line.
• At the sarcolemma, these plaques contact the DGC/DAPC
and a7b1- integrin for interaction with the ECM. These
regions are believed to stabilize domains of the
sarcolemma throughout muscle contraction and relaxation.
• In addition, costameres transmit force laterally in both
resting and active muscle through the sarcolemma via
attachment to the ECM and tendon.

32. NUCLEAR ENVELOPE PROTEINS
• The nuclear envelope is composed of 2 lipid bilayers,
the outer nuclear membrane, which is contiguous with
the endoplasmic reticulum, and the inner nuclear
membrane.
• Positioned within the inner nuclear membrane are a
variety of integral membrane proteins.
• The important ones are- Emerin and lamin A which are
expressed in all differentiated cell types, yet these
diseases specifically affect only a subset of tissues.
• Thus, it was proposed that Emerin and lamin A have
roles in tissue-specific gene expression, cell signaling,
or nuclear structure