introduction to proteins - the atomic structure of proteins

functions of proteins

• cell building blocks, provide shape and structure

• enzymes, catalyze cell chemical reactions

• membrane proteins, form communication channels

• transport of cargo and mechanical forces

structure of amino acids

• amino group (-NH₂)

• carboxyl group (-COOH)

• α-carbon atom

• side-chain group (R)

chemical characteristics of amino acid side chains

• hydrophobic, polar, charged (acidic or basic)

• small or large

• covalently linked into polypeptides

polar amino acids

• asparagine (Asn, N)

• glutamine (Gln, Q)

• serine (Ser, S)

• threonine (Thr, T)

• tyrosine (Tyr, Y)

basic amino acids

• lysine (Lys, K)

• arginine (Arg, R)

• histidine (His, H)

acidic amino acids

• aspartate (Asp, D)

• glutamate (Glu, E)

hydrophobic nonpolar amino acids

• alanine (Ala, A)

• valine (Val, V)

• proline (Pro, P)

• phenylalanine (Phe, F)

• glycine (Gly, G)

• cysteine (Cys, C)

• leucine (Leu, L)

• isoleucine (Ile, I)

• methionine (Met, M)

• tryptophan (Trp, W)

polypeptide backbone

• peptide bond is planar and cannot rotate

• rotation around the bonds to the central carbon (Cα)

  • phi: between Cα and amino group

  • psi: between Cα and carboxyl group

• partial double-bond character → no free rotation

polypeptides

• only L amino acids

• peptide bonds occur in trans configuration (except for P)

non-covalent interactions between residues of a polypeptide that stabilize structure

• hydrogen bonds

• van der Waals interactions

• ionic bonds

• hydrophobic interactions

disulfide bonds

• covalent interaction between cysteines

• often present in secretory proteins to reinforce structure

primary structure of a protein

linear amino acid sequence, determines structure and function

secondary structure of a protein

• local conformation patterns resulting from hydrogen bonding between N-H and C=O groups in backbone

• stretches of polypeptide adopts regular and repeating arrangements

• common structures are α-helices and β-strands/sheets

α-helix

• single polypeptide chain twists around on itself

• backbone is coiled

• hydrogen bonds between carbonyl oxygen and amine hydrogen every 4 peptide bonds

• side chains point outwards

β-sheets

• backbone is extended almost straight

• several strands pack sideways into a sheet

• hydrogen bonds between backbone strands

• side chains on alternate sides

• very rigid structure

• antiparallel or parallel types

tertiary structure of a protein

• complete three-dimensional arrangement of the polypeptide

• secondary structure elements are packed against each other to form tertiary structures

• hydrophobic contacts between secondary elements

• long-range contacts between residues that are far apart in the primary sequence

• loops have no regular secondary structure and can be flexible

quaternary structure

• assembly of multiple polypeptides (subunits) into a final protein

• interactions between subunits are very stable

models for visualizing proteins

• polypeptide backbone

• ribbon diagram (polypeptide backbone only)

• stick diagram (includes amino acid side chain)

• space-filling model (with mass of atoms)

domain

• independently folded unit within a protein

• often have different functions

• modular/conserved domains are found in many proteins in different combinations with other domains, often form reversible, specific, non-covalent contacts with other molecules

polypeptide length

• 100-800 amino acids long

• 12-90 kDa in molecular weight

• domains are usually 50-200 amino acids long

protein interactions

• specific

  • only certain molecular surfaces are bound

• transient

  • interactions form and break apart quickly

• binding equilibria

  • A+B ⇌ A∙B

sequence similarity

• sequences of different polypeptides can be compared to align identical and similar amino acids

• sequence identity and similarity indicate evolutionary conservation and suggest common structure or function

divergent polypeptides

polypeptides that do not have any sequence similarity

conservative substitution

substitution of one amino acid with another with similar properties (ex: asparagine → glutamine)

protein family

• set of proteins or domains with homologous sequences and structures

• often have related functions

• an organism can have several proteins from the same family

• proteins from a family can be found in different organisms