Protein Structure and Function (Chapter 3)

Vocabulary flashcards covering key terms and definitions from the Protein Structure and Function lecture notes.

Conformation

A protein’s three‑dimensional shape; correct folding is critical for function and function derives from this structure.

Primary structure

The linear sequence of amino acids in a polypeptide.

Secondary structure

Local folding patterns such as α helices, β sheets, turns, and random coils.

Tertiary structure

The overall three‑dimensional folding of a single polypeptide, including core packing and long‑range interactions.

Quaternary structure

The assembly of multiple polypeptide subunits into a functional protein complex.

Amino acid

The monomeric unit of proteins; general structure includes an amino group, a carboxyl group, and a variable side chain (R).

Peptide bond

Covalent bond between adjacent amino acids; the C–N bond is planar due to partial double‑bond character.

N-terminus

Amino end of a polypeptide chain.

C-terminus

Carboxyl end of a polypeptide chain.

Peptide

Short chain of amino acids (2–30 residues).

Polypeptide

Long chain of amino acids; a peptide that is longer and has intrinsic information for folding.

Protein

A folded polypeptide (or protein complex) that has a specific, functional conformation.

α-helix

A right‑handed helical secondary structure stabilized by backbone hydrogen bonds; ~3.6 residues per turn.

β-sheet

A secondary structure consisting of β‑strands linked by hydrogen bonds; can be parallel or antiparallel.

β-turn (β turn)

A short turn (~4 amino acids) that reverses the direction of the peptide chain.

Random coil

A region with no defined secondary structure; connects helices and sheets.

Domain

A distinct, modular region of a protein that folds independently and often has a specific function.

Motif

A recurring, defined structural pattern within a protein that can have a particular function.

Coiled‑coil motif

A dimerization motif formed by amphipathic helices with a leucine‑rich heptad repeat.

Leucine zipper

A type of coiled‑coil motif with Leu at every seventh position that mediates dimerization.

EF-hand

A helix–loop–helix motif specialized for Ca2+ binding in many proteins.

Zinc‑finger motif

A DNA‑binding motif coordinated by Zn2+ with cysteines and histidines.

Globular protein

A compact, roughly spherical protein with diverse secondary structures.

Fibrous protein

Elongated, filamentous proteins with extended structures.

Integral membrane protein (IMP)

Protein that spans a membrane, often with hydrophobic transmembrane helices.

Intrinsically disordered protein

Proteins lacking a fixed 3D structure in isolation; can gain structure upon interactions.

Hydrophobic effect

Driving force of folding; nonpolar residues cluster in the core away from water.

Protein folding

Process by which a polypeptide assumes its native, functional conformation.

Chaperone

Proteins that assist folding and prevent misfolding; examples include Hsp70 and Hsp90.

Chaperonin

Barrel‑shaped complexes (e.g., GroEL/GroES) that provide an isolated folding chamber.

Denaturation

Unfolding of a protein due to heat, chemicals, or pH changes; renaturation is possible for some proteins.

Disulfide bond

Covalent linkage (S–S) between cysteines that can stabilize a protein’s folded state.

Cofactor

Non‑protein molecule required for enzyme activity (often metal ions or organic molecules).

Heme

Iron-containing prosthetic group in hemoglobin and myoglobin.

Cofactor vs prosthetic group

Cofactor is a non‑protein helper; a prosthetic group is a tightly bound non‑protein unit like heme.

Heme protein

Proteins that contain a heme group, often involved in oxygen transport or redox chemistry.

Enzyme

Biological catalyst that increases the rate of a chemical reaction.

Active site

Region of an enzyme where substrate binding and catalysis occur.

Substrate

Reactant molecule that binds to an enzyme.

Enzyme–substrate complex (ES)

Transient complex formed when an enzyme binds its substrate.

Induced fit

Model where enzyme changes shape to accommodate substrate and catalyze the reaction.

Allosteric regulation

Regulation of enzyme activity through binding at a site other than the active site, often cooperative.

Cooperativity

Allosteric interaction where binding at one site affects binding at another, often in multisubunit proteins.

cAMP

Cyclic adenosine monophosphate; a second messenger that activates protein kinase A.

Protein Kinase A (PKA)

A cAMP‑dependent kinase; regulatory subunits bind cAMP and activate catalytic subunits.

Calmodulin

Ca2+-binding messenger protein with four EF‑hand motifs; regulates target proteins.

GTPase switch proteins (GTPases)

Proteins that cycle between active GTP‑bound and inactive GDP‑bound forms to regulate signaling.

GEF (guanine nucleotide exchange factor)

Promotes exchange of GDP for GTP on GTPases, activating them.

GAP (GTPase‑activating protein)

Stimulates GTP hydrolysis, inactivating GTPases.

Phosphorylation

Covalent addition of a phosphate group to a protein by kinases; reversible by phosphatases.

Kinase

Enzyme that catalyzes phosphorylation.

Ubiquitin

Small protein that covalently attaches to substrates to signal degradation or regulation.

Proteasome

Cytosolic/nuclear protease complex that degrades ubiquitinated proteins.

E1/E2/E3 enzymes

Enzymes that activate (E1), conjugate (E2), and ligate (E3) ubiquitin to substrates.

Destruction box

Sequence motif in proteins (e.g., cyclins) that targets them for ubiquitination and degradation.

Proteolytic cleavage

Processing of a protein by proteases to activate or generate mature forms.

Native state

The functional, correctly folded conformation of a protein.

Breathing

Small, dynamic fluctuations in a protein’s structure while in the native state.

X-ray crystallography

Technique to determine precise 3D structure by X-ray diffraction from crystals.

Cryo‑electron microscopy (cryo‑EM)

High‑resolution 3D structure determination of biomolecules frozen in vitreous ice.

NMR spectroscopy

Technique using magnetic fields to determine distances between atoms; good for smaller proteins.

Mass spectrometry (MS)

Analytical method to measure mass/sequence information of proteins and peptides.

MALDI‑TOF

Matrix‑assisted laser desorption/ionization time‑of‑flight MS; generates peptide fingerprints.

ESI‑MS

Electrospray ionization MS; useful for analyzing intact proteins and peptides.

LC‑MS/MS

Liquid chromatography coupled to tandem MS; used for proteomics and peptide sequencing.

Proteomics

Large‑scale study of the structure and function of proteins in a system.

SDS‑PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis; separates proteins by size under denaturing conditions.

Isoelectric focusing (IEF)

Separation of proteins by pI along a pH gradient based on net charge.

Two‑dimensional gel electrophoresis

Separation by isoelectric point (IEF) in one dimension and size by SDS‑PAGE in the second.

Gel filtration chromatography

Size‑exclusion chromatography; separates proteins by size.

Ion exchange chromatography

Chromatography that separates proteins by charge; involves anion or cation exchange beads.

Affinity chromatography

Purification based on specific binding to a ligand or antibody.

Western blotting (immunoblotting)

Detecting specific proteins on a membrane using antibodies.

Immunoprecipitation

Isolating a protein by binding it with a specific antibody and precipitation.

Edman degradation

Sequential N‑terminal sequencing of proteins/peptides by removing one residue at a time.

Peptide fingerprinting (mass spectrometry)

Identifying proteins by matching peptide mass spectra to databases.

In vitro peptide synthesis

Chemical synthesis of short peptides for study or antibody production.

Intein (self‑splicing protein)

Protein segment that excises itself and ligates the remaining portions; rare and not on exam.

Homo/heterologous protein families

Proteins sharing ancestry (homologous) with similar sequences and structures.

Homologous proteins

Proteins in related species with similar sequences and structures, indicating common ancestry.

Heme as a cofactor

An iron-containing prosthetic group in certain proteins (e.g., hemoglobin) necessary for function.

Cofactor vs prosthetic group (distinction)

Cofactor is a non‑protein helper; prosthetic group is a tightly bound cofactor essential to function.

Supramolecular assembly

Large assemblies formed by multiple proteins and other molecules functioning as a unit.

Proteolysis vs degradation

Proteolysis is enzymatic cleavage; degradation is breakdown of proteins for turnover.

Isoelectric point (pI)

pH at which a protein has no net electric charge.

Two‑dimensional proteomics workflow

Combination of separation by pI (IEF) and by size (SDS‑PAGE) before MS analysis.

Native conformation

The functional 3D structure in which a protein naturally operates.

Conformational change

Alteration in shape accompanying function, such as during enzyme catalysis or signaling.

Allosteric switch

Noncovalent structural changes that modulate activity in response to ligand binding.

Gliding through the notes: “breathing” and structural dynamics

Non-rigid fluctuations within the native state that can influence function.