Scene 1

Maivel H. Ghattas, M.D. Prof. of Medical Biochemistry

Scene 2

To identify the primary, secondary, tertiary & quaternary structures of proteins. 2) To list the features of a peptide bond. 3) To compare the methods for determining amino acid sequence of a protein. 4) To describe the concept of domain structures in proteins. 5) To describe diseases due to protein misfolding

Scene 3

Scene 4

Scene 5

Primary structure is the sequence of amino acids in protein.

Abnormal amino acid sequence of proteins can lead to disease.

Scene 6

Scene 7

Uncharged (do not give up or accept protons). However, they can form hydrogen bonds.

peptide bond  (Fig. 2.2B) a) has "partial double bond“ characteristics – no free rotation around a peptide bond; rigid and planar b) rotation on either side of  a -carbon can occur (with the exception of pro). Thus, variation in three dimensional structure can occur. c) peptide bond almost always  trans d) groups in amide bond – uncharged (do not give up or accept protons). However, they can form hydrogen bonds (important)

Has “partial double bond”  No free rotation around a peptide bond; rigid and planar.

Scene 8

polypeptides are named with the first a.a being the one with a free   -amino group. "-yl" is used as suffix, except for last (carboxyl) aa. Amino acid sequence with free amino terminus is written to the left, free carboxyl terminus to the right

Scene 9

Scene 10

Rotation on either side of   -carbon can occur (with the exception of pro).

Scene 11

Scene 12

Scene 13

Spiral structure, tightly packed, coiled.  Side chains (R-groups) point outward from spiral. Hydrogen bonds stabilize  the  helix. C=O group of one a.a. forms H bond with NH group of  4th  a.a.

Scene 14

Combination of many weak H bonds cause very stable structure.  All NH and C=O groups are in H bonds, except those in the first and last a.a. in the helix.  3.6 a.a. per 1 turn of the   -helix. results in more compact structure.

Scene 15

proline breaks   -helix because of imino structure. Puts in a kink. Highly charged aa's (asp,glu,his, lys, arg) – many ionic bonds disrupt helix. Many aa's with bulky side chains (trp) or branched side chains (val, ile) disrupt the helix.

Scene 16

H bonds perpendicular to polypeptide backbone Antiparallel or Parallel. Sheet is "pleated" in structure.

Scene 17

Interchain H bonds: between two different polypeptide chains. Intrachain H bonds: between aa's in the same polypeptide chain

Scene 18

 -bend,  (    -turn; reverse turns)

1) reverses direction of polypeptide chain - helps form compact, globular shape. 2) often found on surface 3) often have charged aa's, gly (small, fits), and pro (causes "kink")

Scene 19

Scene 20

Scene 21

Scene 22

Domains: "fundamental functional and 3D structural. A combination of motifs forms a domain. A domain is usually globular. Each domain folds independently of other domains.

Scene 23

Interactions that stabilize tertiary structure 1)  Disulfide bonds:  (two cysteine)  (-SH) oxidize and form a disulfide bond. Can be located on the same polypeptide chain (intrachain) or on different polypeptide chains (interchain). Strong covalent bond that keeps protein folded in a 3D (tertiary) structure)

Scene 24

2)  hydrophobic interactions  : nonpolar groups (generally in interior) associate with themselves and stabilize tertiary Structure. 3)  Hydrogen bonds:  polar uncharged aa's, mostly (C=O, NH)

Scene 25

4)  Ionic interactions  (salt bridges): polar charged amino acids – asp, glu, lys, arg (COO-, NH3+)

Scene 26

Scene 27

Multiple subunits interacting together (2 = dimer; 3 = trimer;4 = tetramer, etc.)  Interactions stabilized by noncovalent bonds (hydrophobic interactions, H bonds, ionic bonds)  Subunits may act independently or cooperatively

Scene 28

Scene 29

side chain interactions of nearby amino acids assist in the rapid folding by maximizing favorable interactions (attractions) but minimizing unfavorable interactions (repulsion). Occurs in a local, orderly, stepwise fashion

Scene 30

Prevent improper or early folding when protein synthesis is occurring. 1) many of these are "heat shock" proteins induced by stress. Help refold some proteins 3) if large proteins are denatured, they will often not properly fold even with chaperones present.

Scene 31

A) Unfolding and disorganization of protein structure. B) Peptide bonds NOT broken C) Heat, organic solvents, detergents, physical agitation, heavy metals.

Scene 32

D) urea, guanidine hydrochloride, Pb, Hg. E) Once denatured proteins rarely renature properly. Exceptions  (ribonuclease).

Scene 33

Abnormal proteolytic cleavage can generate protein fragments that can form  b -pleated sheets and then associate to form long fibrous aggregates called amyloids. Alzheimer’s Disease  amyloid plaques in brain .

Scene 34

Transmissible disease, but the infectious agent is NOT a nucleic acid (DNA, RNA) as is true in virally transmitted diseases. The agent is a  misfolded protein  (PrP)!!

Scene 35

Scene 36

Scene 37

Enzymes       Enzymes are mainly proteins Hormones      peptides (glucagon) or protein (insulin) Structural proteins      Collagen and elastin

Scene 38

Defense mechanisms       Immunoglobulins (Ab)       Keratin of the skin Transport  Carrier of molecules Hb , Plasma lipoproteins, Glucose        transporters

Scene 39

Cell membranes       contain proteins Storage      Ferritin the storage form of iron

Protein Structure

Page 1 (0s)

Page 2 (12s)

Page 3 (40s)

Page 4 (2m 36s)

Page 5 (2m 42s)

Page 6 (3m 46s)

Page 7 (4m 11s)

Page 8 (4m 53s)

Page 9 (5m 38s)

Page 10 (6m 53s)

Page 11 (7m 42s)

Page 12 (7m 47s)

Page 13 (7m 51s)

Page 14 (9m 34s)

Page 15 (10m 26s)

Page 16 (12m 7s)

Page 17 (14m 27s)

Page 18 (14m 38s)

Page 19 (15m 52s)

Page 20 (17m 25s)

Page 21 (17m 35s)

Page 22 (17m 43s)

Page 23 (17m 51s)

Page 24 (19m 27s)

Page 25 (20m 44s)

Page 26 (21m 49s)

Page 27 (22m 1s)

Page 28 (22m 5s)

Page 29 (22m 10s)

Page 30 (23m 36s)

Page 31 (25m 44s)

Page 32 (26m 38s)

Page 33 (26m 44s)

Page 34 (28m 41s)

Page 35 (29m 49s)

Page 36 (30m 9s)

Page 37 (30m 25s)

Page 38 (31m 21s)

Page 39 (32m 7s)

Page 40 (32m 35s)