Protein Structure-Function Relations and Motor Proteins

Vocabulary flashcards covering the structure and function of oxygen transport proteins (myoglobin and hemoglobin) and motor proteins involved in muscle contraction (actin and myosin).

Myoglobin (Mb)

A monomeric globular protein consisting of an $\alpha$-helix-rich polypeptide chain and a heme prosthetic group, which stores oxygen in muscle tissue and exhibits high oxygen affinity.

Hemoglobin (Hb)

A tetrameric multimeric protein consisting of four subunits ($\alpha_2\beta_2$ in adults) held by non-covalent interactions, which transports oxygen from lungs to tissues and displays allosteric cooperativity.

Heme

A non-peptidic, cyclic, polar, and planar prosthetic group containing a ferrous iron atom ($Fe^{2+}$) capable of forming 6 coordination bonds (4 with the heme ring and 2 with histidine residues or oxygen).

Proximal Histidine

An amino acid residue from myoglobin or hemoglobin that directly coordinates with the $Fe^{2+}$ atom of the heme group.

Distal Histidine

An amino acid residue in myoglobin and hemoglobin located near the heme group between which molecular oxygen ($O_2$) intercalates to coordinate with the $Fe^{2+}$ atom.

Cooperativity

An allosteric phenomenon in hemoglobin where the binding of one $O_2$ molecule to a subunit increases the oxygen binding affinity of the remaining subunits, resulting in a sigmoidal saturation curve.

$$P_{50}$$

The partial pressure of oxygen at which a protein is $50\%$ saturated; it serves as an inverse measure of oxygen affinity ($3\text{--}5\,\text{torr}$ for myoglobin and $26\,\text{torr}$ for hemoglobin).

Torr Conversion Factors

Standard pressure conversions where $1\,\text{torr} = 1\,\text{mmHg} = 0.13\,\text{kPa}$.

Bohr Effect

The physiological mechanism where increases in $CO_2$ partial pressure or decreases in pH (increased $H^+$ concentration) increase $P_{50}$, reducing hemoglobin's oxygen affinity to promote $O_2$ release in metabolically active tissues.

2,3-Diphosphoglycerate (2,3 DPG)

A glycolysis intermediate that binds to the central cavity of hemoglobin specifically in its T state, stabilizing the low-affinity conformation and enabling subunit cooperativity.

T State (Tense State)

The low-oxygen-affinity quaternary conformation of hemoglobin that predominantly corresponds to the deoxygenated form and is stabilized by 2,3 DPG.

R State (Relaxed State)

The high-oxygen-affinity quaternary conformation of hemoglobin that predominantly corresponds to the oxygenated form.

Symmetric Model ('Tout ou Rien')

An allosteric model of hemoglobin where all four subunits transition simultaneously from the T state to the R state upon oxygen binding.

Sequential Model

An allosteric model of hemoglobin where each subunit transitions individually and progressively from the T state to the R state as it binds an $O_2$ molecule.

Carbon Monoxide (CO)

A competitive inhibitor that blocks the $O_2$ binding site on myoglobin and hemoglobin by binding to the heme iron with a higher affinity than oxygen.

Methemoglobin (Ferrihemoglobin)

An inactive form of hemoglobin resulting from the oxidation of ferrous iron ($Fe^{2+}$) to ferric iron ($Fe^{3+}$), which can only form 5 coordination bonds and cannot bind oxygen.

Fetal Hemoglobin (HbF)

A fetal hemoglobin variant composed of $\alpha_2\gamma_2$ subunits that has a higher oxygen affinity than maternal adult hemoglobin ($HbA$) because its $\gamma$ chains have lower affinity for 2,3 DPG.

Sickle Cell Hemoglobin (HbS)

A mutant hemoglobin caused by a single amino acid substitution in the $\beta$ subunit that exposes a hydrophobic pocket upon deoxygenation, causing polymerization into falciform red blood cells without destroying the active oxygen-binding site.

Sarcomere

The basic contractile unit of a muscle cell composed of thin filaments containing G-actin and thick filaments containing myosin.

G-actin (Globular Actin)

A monomeric, globular, polarized protein containing bound ATP and a $Ca^{2+}$ ion (which participate in actin polymerization) that forms actin filaments.

Myosin

A $520\,\text{kDa}$ motor protein composed of 6 subunits: 2 heavy chains ($2 \times 220\,\text{kDa}$) forming a double $\alpha$-helical supercoiled tail, and 2 pairs of light chains ($2 \times 2 \times 20\,\text{kDa}$) forming two head domains.

S1 Fragment (Myosin Head)

The motor domain of myosin produced by enzymatic cleavage that contains ATPase enzymatic activity and an actin-binding site, functioning as a lever arm to slide actin filaments.

Tropomyosin

A regulatory protein that wraps around the actin filament in the absence of calcium to mask the myosin-binding site.

Troponin Complex

A three-subunit regulatory protein complex composed of subunit T (binds tropomyosin), subunit C (binds calcium), and subunit I.

Troponin Subunit C (Troponin C)

The calcium-binding subunit of troponin that undergoes a conformational change upon binding $Ca^{2+}$, shifting the troponin-tropomyosin complex to expose myosin-binding sites on actin.

Sarcoplasmic Reticulum (REL)

The smooth endoplasmic reticulum of myocytes that stores calcium ions and releases them into the cytoplasm via voltage-dependent calcium channels following T-tubule depolarization.