Biochem Exam 2: Muscle Contractions

L17

Actin microfilaments

plays a part in changing cell shape, cell division, endocytosis, small molecule transport

ATP Hydrolysis

major role in muscle movement

• ex) separation of chromosomes, beating of flagella, cell migration, muscular contraction

Amoeboid motion

1. ATP-G binds both F-actin ends (ATP-G has great affinity for + end)

2. Binding activates F-actin subunits to hydrolyze ATP

3. ADP-F-actin conformation change → leads to lower affinity for neighboring subunits

4. Rate of ATP hydrolysis by F-actin is lower than rate of polymerization → polymer grows as ATP-actin subunits added to + end (pushing force)

Treadmilling

when rate of association of new G-actin molecules in the + end equals rate of disassociation from - end

Voluntary muscles

striated appearance under light microscopy

• consist of long, multinucleated cells (muscle fibers)

• muscle fibers contain parallel bundles of myofibrils

Sarcomere

myofibril repetitive unit

• included between 2 Z disks

• contains A bands (thick filaments) + I bands (thin filaments) which are linked via cross bridges

• contractions reduce the length of I band and H zone

Sliding filament model (Hugh Huxley)

observations where overlapping thick (A bands) & thin filaments (I bands) slid past each other

• thick filaments consist of Myosin

• thin filaments mainly Actin and a little Tropomyosin + Troponin

Myosin

consists of 6 polypeptide chains

• two heavy chains: each w/ N-term globular head (where ATP hydrolysis and interactions w/ actin occur) and a-helix tail → form left-handed coil

• tail sequence: 7 AA repeat w/ hydrophobic residues at position 1 + 4

• ELC + RLC binds each heavy chain

Myosin under physiological conditions…

several hundred myosin aggregate to form thick filaments

• the heads (have ATPase activity) form cross bridges w/ the thin filaments

Actin

part of the thin filaments

• exists as 375 AA long monomer (G-actin) or polymer F-actin

• each subunit has binding sites for ATP, Ca2+, Mg2+

• + end binds w/ Z disk

• ATPase and Ca2+ binding are NOT relevant to muscle contraction

Tropomyosin

homodimer w/ 284 residues

• contains several a-helices → fold into parallel coiled coil which masks myosin binding site of actin

Troponin

composed of TnC (Ca2+ binding protein), TnI, TnT

• Ca2+ displaces myosin binding site in actin

Dystrophin

reduces stress of muscle membrane upon contraction

• if mutated → Duchenne muscular dystrophy and Becker muscular dystrophy

Ca2+ Mechanism

1. Nerve impulse stimulates myofibril → releases Ca2+ (from sarcoplasmic reticulum)

2. Ca2+ induces conformation change in tropomyosin-troponin complex → exposes site of actin for myosin binding

3. Ca2+ pumped back → tro-tro complex resumes resting conformation → blocks myosin binding to actin (muscle relaxation)

IgM (antibody)

most effective against microorganisms; 1st to be secreted

IgA (antibody)

present in intestines; blocks adhesion of pathogens to epithelia

IgG (antibody)

most common; equally present in blood and extravascular fluid

IgE (antibody)

protects against parasites, allergic rxns

IgD (antibody)

unknown function

Antigens

small foreign, non-self molecules that activate immune system

• recognized by immunoglobulins

Antibodies (IgG) and antigens

each antibody (IgG) binds 2 identical antigens (divalent molecules) → leads to formation of antibodies cross-linked to antigens

Antibody structure

Ig contains 2 identical light chains + 2 identical heavy chains

• subunits connected via di-S bonds

Strength of antibody-antigen interactions determined by:

1. van der Waals

2. hydrophobic interactions

3. h-bonding

4. ionic interactions

Immunoglobulin fold

sandwich of three-four-stranded antiparallel B-sheets linked by di-S bond

• has 3 hypervariable loops → to recognize multiple antigens

Somatic hypermutation

permits fine tuning of antigen specificity of antibody