Protein Structure

protein structure is the 3-D shape polypeptides take on

• primary structure: squence of polypeptides

• secondary structure: alpha helixs and beta pletead sheets

• tertiary structure: is fully folded 3-D shape of a polypeptide

  • myoglobin: final is this strucutre

• quaternary structure: final shape of protein, can be made up of subunits

  • subunits: fully folded tertiary structure of single polypeptide

    • hemoglobin have subuints

carbon has tetrahedral geometry: with angle of 109.5 degrees

aminos acids have chirality

• chirality: not identical to its mirror image

• stereoisomers: molecules with same chemical bonds but different arrangement of them in space

in nature amino acids are found in L form

• some D-amino acids are found in bacterial walls

glycine is achiral because its R group is another H

discerning between L & D amino acids

• clockwise spelling when H is pointing toward you is in L form, spells CORN

  • carboxyl, R group, amino group

• if counter clockwise is D amino acid

3-D drawing

• wedges project out towards you

• dashes point backwards

• line is in line with plane

3-D polypeptide

• r groups are in opposite directions, trans configuration

  • favored as R groups are not hindering one another

• can fold in cis configuration (same) but would hinder each other

• peptide bonds with proline form in cis configuration 3-10%

• each resiude retains tetrahedral shape

  • main carbon atoms lie within same plane

key features of polypeptides

• bond that joins alpha Carbon to carbon of carbonyl is psi bond

  • trident symbol

• bond that joins alpha carbon to amide is phi bond

  • symbol of circle with capital i through it

• trans config when both phi and psi bond have 180 degree rotation

  • alternating r groups

• cis config when both phi and psi bonds have 0 degrees rotation

  • r groups on same side

• conformational flexibility for protein comes from 360 degree rotation around phi and psi bonds

• peptide bond is planar as protein folds and rigid

  • due to partial double bond character amide

  • N can donate electrons to C which pushes them to O resulting in

    

  • amides have resoance

  • creates the double bond which are rigid so no rotation

polypeptide can be viewed as series of rigid planes that can rotate at alpha carbon

Secondary protein structure

• forms as a result of polypeptides maximizing the number of H-bonds it can make between its carbonyls and amides from its backbone

• common type is alpha helix and beta pleated sheet

  

• alpha helices: coiled portion of polypeptides, result of carbonyl of eariler residue H bonds with amide of the later residue that is 4 away

  • called n+4 rule

  • makes a complete turn every 3.6 residues

  • R groups are positioned 100 degree angle from one another

    • 360 degree rotation has 3-4 residues

  • have a right hand turn like screws

    • on a right handed spiral staircase you can keep your right hand on the bannister and go down them the whole time

  • myoglobin made of 7 alpha helices

  • carbonyl’s point down and amides point up

    • perfect H-bond

  • hydrophobic portion of protein (R group) point inward

  • hydrophillic point outward and interact with aqueous solvent

  • not a hard rule but every 3-4 residues share polarity

  • Pro and Gly least likely to be a part of alpha helix

  • don’t have prolines

    • can’t Hydrogen bone so presence creates a destabilizing kink

  • amino acid residues with oppsite charges found 3-4 resiudes away, are stabilizing due to favorable electrostatic attraction

  • amino acid residues with same charges found 3-4 residues away can be destabilizing due to unfavorable electrostatic repulsion

  • amino acid residues with bulky R group found 3-4 residues away can be destabilizing due to steric hinderance

• beta pleated sheets

  • form when two or more polypeptides H bond with each other; two forms anti-parallel and parallel

    • anti-parallel: happen when polypeptide folds in on itself, explains the direction of protein

      • H bonds occur between carbonyl and aimdes

      • two strands run in opposing direction (like DNA)

    • parallel: need a lot more polypeptide between the two starands to make the sheets line up in parallel fashion

  • pleats happen from alpha carbons fully extending and alternating up and down

    • r groups do this to

    • porin made of beta pleated sheets

      • found in bacteria cell membrane for transport of stuff

        • antiparallel shape

  • result of extended polypeptide, R groups point in opposite directions

  • beta turns (tight turns): connect 2 antiparallel strands together(makes 180 degree turn)

    • Hydrogen bond between 3 residues away

    • proline and glycine often found

    • imino nitrogen of Pro can take on the cis from which makes for a tight turn

    • can’t connect two parallel strands

• helps fully understand its job

steric hinderence: when atoms/molecules try to take up same space it causes electron clouds to overlap, causing repulsive force and influences which bond angles are more likely to occur

• not favorable

tertiary structure: refers to 3-D arrangement of all atoms in folded polypeptide; may be the final protein of it may be subunit of complete final protein

• folds upon itself, may include alpha helix and beta pleated sheets

• secondary and tertiary structures began to take form as the ribosome is folding the translating

• sequence is responsible the protein folding

• native conformation is the folded and functional form of the protein

• denature state, is the unfolded and there is no activity or function

  • can happen due to

    • temperature increase

    • pH increase/decrease

    • salt concentration changes

    • solvent changes

  • doesn’t break covalent bonds in polypeptide (order is preserved) interferes with IM interactions

• anfinsen’s dogma: 3D structure determined by seqence of amino acids

  • even if protein was denatured they can still refold

• the unfolded protein in entropically favorable, as it has more disorder

  • protein folding is an energtically favorable process due to gibbs free energy

    • delta G = delta H - TdeltaS

      • negative gibbs free energy means reaction is spontaneous/exergonic

      • positive gibbs free means reaction is non-spontaneous/endogonic

      • negative enthalpy means exothermic

      • positive enthalpy means endothermic

      • negative entropy means more ordered

      • positive entropy means more disordered

  • things that make protein folding entropically favorable

    • hydrophobic effect: exergonic; biggest factor that makes protein folding happen

      • unfolded is entropically favorable for polypeptide but unfavorable for water around because of non polar R groups

        • Clathrate: water molecules encaging a nonpolar solute very order bad for entropy, but folding means breaking free of this as the non polar R group fold inside and polar are outside better for water

      • overcomes the entropy

    • formation of new IMF and disulfide bonds: collectively contribute

      • makes the enthalpy negative

        • IMF

          • ionic attraction: strongest

            • occur between R groups of positive and negative charged

          • H-bonds: less strong then inonic

            • secondary structures, R groups, R groups and polypeptide amides/carbonyls unused in secondary structures

          • Van der Waals: weakest force of all, but can collectively contribute; NP molecules take on temporary dipoles

            • between NP groups in center of protein

            • can be ion-Induced Dipole, dipole induced dipole, dispersion

        • Di-sulfide bonds between cysteines

          • not IMF interaction

          • occurs between two cysteines

quaternary structure: final protein made up of 2 or more subunits

• each subunit is its own polypeptide that folds into its own tertiary structure

• subunits may be identical or may be different

• hydrophobic effect and IMF keep the subunits togethers