Protein Structure and Function: Membrane-Bound Proteins and Biosignaling

What distinguishes primary, secondary, tertiary, and quaternary structure?

Primary is the amino acid sequence; secondary is local backbone structure; tertiary is the 3D fold of one chain; quaternary is the assembly of subunits.

Why are α-helices and β-sheets called secondary structure, and what mainly stabilizes them?

They are regular local backbone arrangements, held mainly by hydrogen bonds between backbone carbonyl C=O and amide N–H groups.

What happens to heme Fe²⁺ when O₂ binds, and how does that local event affect the whole tetramer?

O₂ binding pulls Fe²⁺ into the heme plane, moving His F8 and helix F and shifting the tetramer from the low-affinity T state toward the high-affinity R state.

Why can hemoglobin bind O₂ cooperatively?

Its subunits interact. Binding O₂ at one subunit shifts the whole tetramer toward R, making the next O₂ easier to bind.

Trace the HbS sequence from deoxygenation to impaired blood flow.

Deoxygenation → hydrophobic HbS contacts → polymerization into rigid fibers → sickling and reduced deformability → small-vessel obstruction and impaired flow.

What are the two separate ways CO reduces effective O₂ delivery?

CO occupies heme sites (lower O₂ capacity) and favors the R state of the remaining sites (a left shift), so bound O₂ is released less readily.

Why can a standard pulse oximeter be misleading in CO exposure?

Standard pulse oximetry cannot separate oxyhemoglobin from carboxyhemoglobin, so the reading may not reflect true O₂ delivery. Confirm CO exposure with blood co-oximetry.

Rank these from easiest to hardest to cross a pure lipid bilayer: O₂, H₂O, glucose, Na⁺.

O₂ crosses most readily, then H₂O, then glucose; Na⁺ is essentially impermeable without a protein.

How does a channel differ from a carrier protein?

A channel is a selective pore; a carrier binds its substrate and changes conformation during transport.

What is the conceptual difference between a membrane transporter and a cell-surface receptor?

A transporter moves a molecule or ion across the membrane. A receptor transmits information across it; the ligand doesn’t need to cross.

Name the four receptor families and the key mechanism of each.

GPCR activates a G protein; RTK activates kinase/phosphorylation signaling; ligand-gated ion channel opens an ion channel; intracellular receptor binds a membrane-permeant ligand and the complex regulates transcription.

Trace the albuterol β₂ pathway from receptor activation to bronchodilation.

Albuterol → β₂ receptor → Gs activation → adenylyl cyclase → ATP to cAMP → PKA → protein phosphorylation → bronchodilation.

What is cAMP, what enzyme lowers it, and what happens to cAMP signaling if that enzyme is inhibited?

cAMP is a second messenger. Phosphodiesterase converts it to 5′-AMP. If that enzyme is inhibited, cAMP stays elevated longer and PKA signaling is prolonged.

What structural levels does heat denaturation usually disrupt, and what level usually stays intact?

Heat can disrupt secondary and tertiary structure, and quaternary structure when present; primary structure usually remains intact. Proteolysis, in contrast, breaks peptide bonds.