Protein Structure & Function

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In principle: Proteins are polymers of amino acids

[sometimes NH₃⁺ & COO^- : depends on pH]

     R = radical group determines biological properties: 20 types (note 1- & 3-letter codes)

Group properties	Three- & Single-letter codes
neutral, non-polar  (hydrophobic]	gly, ala, val, leu, ile, pro, met, phe, trp
	G    A    V    L    I    P    M     F    W
neutral, polar (hydrophilic)	ser, thr, cys, tyr, asn, gln
	S    T    C    Y    N    Q
polar basic  (positive charge)	lys, arg, his
	K    R    H
polar acidic (negative charge)	asp, glu
	D    E

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in vitro dehydration of carboxyl & amino termini forms peptide bond

in vivo Peptidyl Transferase catalyzes condensation reaction: H₂0 not lost
carboxyl (C) terminus of growing polypeptide in P site
            cleaved from tRNA &
joined to amino (N) terminus of new amino acid in A site

                => amino end unchanged, carboxyl end "grows":

    Repeating backbone subunit [N - C(R) - C ] is amino acid residue

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Proteins have four levels of structure

Primary Structure - order of amino acid residues in polypeptide
                20^N possible orders with N residues

Secondary Structure - configuration of [-N-C(R)-C-] backbone
        alpha helix: a right-handed helix
beta-pleated-sheet: parallel / anti-parallel chains
both stabilized by H-bonds

Tertiary Structure - 3-Dimensional folding of backbone
Cys + Cys pairs form disulfide bridges ( - S - S -)
        Pro residues form hydrophobic "corners"
hydrophilic residues occur on exterior,
                participate in reactions in aqueous environments
hydrophobic residues occur in interior,
                interact with membrane lipid bi-layer

Quaternary Structure - assembly of multiple subunits
            dimers / tetramers / oligomers
               e.g., hemoglobin is a tetramer: two alpha + two beta chains
           charged residues (Asp, Glu, Lys, Arg, His) form ionic bonds bx subunits

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Post-translational processing
Chemical modification of amino acids
          addition of formyl group to Met  fMet
   Addition of carbohydrate side chains (glycosylation)
e.g., ABO blood group antigen proteins
   Amino acids may be cleaved out of primary structure
e.g., biologically active insulin is less than half the primary  sequence

preproinsulin proinsulin insulin
        (110 aa's)            (86 aa's)        (51 aa's)

HOMEWORK #14: The Case of the Insolent Insulin

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Overview of protein function

Enzymatic catalysis of biological reactions

Substrates are bound in active sites: the Induced-Fit Model
        Lowered energy of activation
            biological rxns occur at body temperature
                                                     with lower energy input
           cf. Thermophillic hot spring bacteria live in 95^oC H₂0

        Identification of recurrent motifs allows inferences about function
Helix - turn - helix motif binds Ca⁺⁺
Zinc - finger motif binds major & minor DNA grooves
Leucine Zipper motif binds DNA and forms 'zippable' dimer

    Other protein functions
Structural
Collagen constitutes 25% of human protein
Histones are the major components of chromosomes

Nucleic Acid binding
Polymerases, nucleases, helicases, ligases, etc.

    Transport
    Hemoglobin in blood & myoglobin in muscle bind O₂

Drosophila Genome Project has cataloged 17,215 genes [Ensembl73 assembly]
            ~50% of Drosophila genes have human homologs
~75% of human genetic disease-associated genes have Drosophila homologs

      The Human Genome comprises 20,050 protein-coding genes: why so few?
                Protein-coding exons may be transcribed in different combination from different promoters
heterogeneous nuclear RNAs (hnRNAs) may be spliced together (introns spliced out) in different mRNA combinations

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All text material ©2024 by Steven M. Carr

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