Protein Domains, Motifs, Structure, and Function

Sequence of amino acids

Primary structure

Local folding (e.g., alpha-helix, beta-pleated sheet)

Secondary structure

Long-range, overall 3D folding of a single polypeptide

Tertiary structure

Multimeric organization of two or more polypeptides

Quaternary structure

Represents large-scale assemblies of proteins

Supramolecular structure

Short patterns/sequences of amino acids (minimum length is 4 amino acids, but most are much larger)

Motif

Represents an amino-acid sequence pattern that is widespread and is conjectured to have a biological significance by function

Motif

Their structure is super-secondary/secondary

Motif

Motifs are __________ than domains

Smaller

Motifs are not _______ independently

Stable

Motif function is typically ____________

Structural

Examples are helix-loop-helix, zinc-finger, and coiled-coil

Motif

The amino-acid __________ dictates motifs

Sequence

Larger regions of proteins that often have a specific function

Domains

Their structure is tertiary and they are larger than motifs

Domains

Domains are _________ independently

Stable

Domains have more __________ functions

Diverse

Domains can consist of __________ motifs

Multiple

Include regulation, signaling, transport, catalysis, movement, and structure

Protein functions

Shows how the protein is packed into the smallest space/volume

Backbone trace

Shows the location of all atoms

Ball and stick

Shows how beta-sheets and alpha-helices are organized

Ribbons

Reveals the actual topography, or lumps and bumps, of the protein

Solvent-accessible surface

Short, recurrent super-secondary/secondary structure patterns of amino acids that are not independently stable, serving primarily structural roles

Motifs

Consists of two alpha helices connected by a short loop; found in calcium-binding proteins and DNA binding proteins

Helix-loop-helix

A Zn+2 ion is held by residues like Cys and His; structure is often formed by two beta-sheets and one alpha-helix; found in many DNA binding proteins and enzymatic proteins

Zinc finger

Consists of two alpha-helices coiled around each other; helix packing is held together by interactions between hydrophobic side chains; found in many DNA binding and transcription factor proteins

Coiled coil motif

Coiled coiled motif is held together by interactions between ___________ side chains

Hydrophobic

A unit of organization distinct from the four levels of protein folding

Domain

Different domains are structurally ___________ and associated with different and specific functions

Independent

Domains can ________ independently into a compact stable structure

Fold

Domains often form _________ units and can consist of multiple motifs

Functional

Functions include catalytic activity, regulatory, locomotion, transport, structural, binding, and formation of assemblies

Domains

The primary _________ of amino acids is the primary determinant of protein folding, and thus, shape

Sequence

The protein folds into various conformations, with the _______ conformation being the most stable

Native

Protein folding is assisted by molecular ___________, which are also proteins

Chaperones

Chaperones _______ ___ folding, prevent misfolding, prevent protein aggregation, and help refold denatured/incorrectly folded proteins

Speed up

Chaperones guide folding along the most energetically favorable path, stabilize partially folded proteins and shield __________ regions to prevent unwanted interactions

Hydrophobic

Smaller chaperones

Chaperonins

A major class of molecular chaperones; their expression increases when cells are exposed to heat and/or stress; always expressed at a low level in normal conditions

Heat shock proteins

An unfolded polypeptide enters the __________ from one end

Chaperone

A cap attachment causes the cylinder to change shape, creating a _________ environment for the polypeptide to fold

Hydrophilic

Mutations that change an amino acid make it difficult for the protein to find its ________ state

Native

A ___________ change in a normal protein results in a misfolded, disease-associated protein

Conformational

The _________ protein can lead to a loss of biological function, aggregation, or gain of toxic activity

Misfolded

Caused by a mutation that changes a single amino acid in the protein chain; a change from glutamate to valine causes hemoglobin to misfold, resulting in sickled red blood cells

Sickle cell anemia

A progressive, fatal condition characterized by the accumulation of Beta-amyloid plaques and hyperphosphorylated tau tangles in the brain

Alzheimer’s disease

The loss of 3D shape, which renders the protein biologically inactive

Denaturation

Caused by environmental factors, including pH, temperature, salt concentration, organic solvents, metal ions, detergents, reducing agents, and mechanical stress

Denaturation