Download MBBS Biochemistry PPT 83 Structure Of Proteins Lecture Notes

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Structure of Proteins

Specific learning objectives

? Structure organization of the Proteins includes:
1) Primary structure (covered in previous lecture)

2) Secondary Structure

3) Tertiary Structure

4) Quaternary Structure
Secondary Structure of Proteins

? Local, regular arrangements of the protein chain are stabilized by hydrogen

bonding.

? Polypeptide chains fold into regular structures such as the alpha () helix, beta ()

sheet, and turns and loops.

? -helices, -strands, and turns are formed by a regular pattern of hydrogen

bonds between the peptide N-H and C=O groups of amino acids (aa) that are near

one another in the linear sequence. Such folded segments are called secondary

structure.
Alpha Helix Is a Coiled Structure Stabilized by Intrachain Hydrogen Bonds

Amino terminus

? The -helix is stabilized by intrachain hydrogen

bonding between the NH and CO groups along

parallel to the helical turn.

? The R groups of each aminoacyl residue in an -

helix face outward.

? Pitch of the -helix: length of one complete turn

along the helix axis and is equal to the product of

the rise (1.5 ?) and the number of amino acid per

turn (3.6), or 5.4 ?.

Fig.4.4 b: Bal -and-stick model of a right handed helix. Lehninger

Principles of Biochemistry

Cont--

Largely -helical protein: Ferritin

? ~75% of the residues in ferritin, a protein

that helps store iron, are in a helices.

? ~25% of all soluble proteins are composed

of a helices connected by loops and turns

of the polypeptide chain.

Fig.2.28: Biochemistry 7th edition by Berg, Tymoczko and Stryer

? Many proteins that span biological

membranes also contain -helices.
Ramachandran diagram for helices

? Right-handed helices are energetical y more

favorable because there is less steric clash between

the side chains and the backbone.

? Amino acids favored: Met, Ala, Leu, Glu, Lys. Amino

acids not-favored: Bulky aromatics, -branched,

those compete with the backbone of H-bond (Ser,

Asp, Asn), and also proline and glycine.

? Polypeptide backbone of an helix is twisted by an

equal amount about each -carbon with a phi ()

angle of -60? and a psi () angle of -47?.

Fig.2.26: Biochemistry 7th edition by Berg, Tymoczko and Stryer

-Sheets Stabilized by Hydrogen Bonding Between Polypeptide Strands

? Distance between adjacent amino acids

along a strand is approximately 3.5 ?.

C

N

C

H

? The side chains are above and below the

O

plane of the strands.

Fig.2.30: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Paral el -sheet

? In the parallel arrangement, for each

aa, the NH group is hydrogen bonded

to the CO group of one aa on the

C

adjacent strand.

R

N

C

H

O

? 1:2 H-bond pattern: 1 a.a bonds with

2 other a.a in an opposing stand.

Fig.2.32: Biochemistry 7th edition by Berg, Tymoczko and Stryer

Antiparal el -sheet

? Adjacent chains in a sheet can run in

opposite directions (antiparallel

sheet) or in the same direction (parallel

C

C

N

sheet).

H

O

? Follow 1:1 H-bond pattern.

? In the antiparallel arrangement, the NH

group and the CO group of each aa are

respectively hydrogen bonded to the

Fig.2.31: Biochemistry 7th edition by Berg, Tymoczko and Stryer

CO group and the NH group of a

partner on the adjacent chain.
Ramachandran diagram for Beta strands

? Ramachandran angles occupy the upper quadrant

(=-135? and =+135?).

? The pink area shows the sterically allowed

conformations of extended, -strand like

structures.

? -strand is extended rather than being tightly

coiled as in the -helix.

Fig.2.29: Biochemistry 7th edition by Berg, Tymoczko and Stryer

Protein rich in -sheet

? Fatty acid-binding proteins (FABP),

important for lipid metabolism, are

built almost entirely from -sheets.

Fig.2.35: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Reverse Turns

? In compact globular proteins, a polypeptide

often makes a sharp turn.

? They cause packing and make it possible for

the molecule to become globular.

? Turns connect helical twists and sheets.

N

H

C

O

? The structure is a 180? turn involving four aa

residues, with the CO of the residue i forming a

hydrogen bond with the NH of the residue i+3.

Fig.3.42: Biochemistry 7th edition by Berg, Tymoczko and Stryer

Cont--

? Loops are responsible for chain reversals and

overal shape.

? Turns and loops invariably lie on the surfaces of

proteins and participate in the recognition role

of proteins, such as the recognition of specific

antigens by antibodies.

? Ex. part of antibody molecule has surface loops

(shown in red) that mediate interactions with

other molecules.

Fig.3.43: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Special types of helices are present in the two proteins

1. -keratin is an elongated -helix. Pairs of

these helices are interwound in a left-handed

sense to form two-chain coiled coils.

? These combine in higher-order structures

called protofilaments and protofibrils.

? About four protofibrils--32 strands of -

keratin altogether--combine to form an

intermediate filament.

? Contribute to the cell cytoskeleton (internal

scaffolding in a cell), and the muscle proteins

Fig.4.11: Biochemistry 7th edition by Berg, Tymoczko and Stryer

myosin and tropomyosin.

Cont--

2. Col agen is the main fibrous component of skin,

bone, tendon, cartilage, and teeth.

? Glycine appears at every third residue in the

amino acid sequence.

? Hydrogen bonds within a strand are absent.

Helix is stabilized by steric repulsion of the

pyrrolidine rings of the proline and

hydroxyproline residues.

Fig.2.40: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Cont--

? Importance of the positioning of glycine inside the triple helix is il ustrated in

osteogenesis imperfecta. In this condition, other amino acids replace the internal

glycine residue.

? The -OH groups of hydroxyproline residues participate in hydrogen bonding, and

the absence of the -OH groups results in the disease scurvy.

Tertiary Structure of Proteins
Tertiary Structure: Water-Soluble Proteins Fold Into Compact Structures with Nonpolar Cores

? The tertiary structure of a protein is its 3-

D arrangement; that is, the folding of its

2?structural elements, together with the

spatial dispositions of its side chains.

? Ex. myoglobin carried out by John

Kendrew and his colleagues in the 1950s.

? Myoglobin, the oxygen carrier in muscle.

It functions both to store oxygen and to

facilitate oxygen diffusion in rapidly

Fig.3.44 b: Biochemistry 7th edition by Berg, Tymoczko and Stryer

contracting muscle tissue.

? Capacity of myoglobin to bind oxygen depends on the presence of heme, a non-

polypeptide prosthetic group consisting of protoporphyrin IX and a central iron

atom.

? The interior consists of nonpolar residues such as leucine, valine, methionine,

and phenylalanine.

? The only polar residues inside are two histidine residues, play critical roles in

binding iron and oxygen. The outside of myoglobin, consists of both polar and

nonpolar residues.
? Principles of the Protein structure:
1. Hydrophobic amino acid side chains located interior of the protein and

hydrophilic side chains are located on the exterior of the protein.

2. Structure: Devoid of symmetry (globular).

3. Tightly packed.

4. Tertiary structure also include disulfide bonds.

Cont---

5. Polypeptide chains folded into a spherical or globular shape. Globular proteins

are stabilized by all weak interactions:

a) Hydrogen bonds
b) Hydrophobic interactions
c) Ionic interactions: Negatively charged groups, such as the carboxylate group (?

COO?) in the side chain of aspartate or glutamate, can interact with positively

charged groups such as the amino group (? NH3+) in the side chain of lysine.

d) Vander wal 's forces: Contribute to both the packing of atoms in proteins as well

as the space between atoms.
Cont---

6. Tertiary structure can be sub-divided into domains:
? Part of protein sequence and structure that can evolve, function, and exist independently

of the rest of the protein chain. , ex. ligand binding domain, membrane spanning domain.

? Protein domain is a conserved part of a given protein sequence and tertiary structure

that can evolve, function and exist independently of the rest of the protein chain.

? Independently folded portion of the protein linked by helical hinges.

? Evolutionary conserved structure common in many proteins.

Cont--

? Many proteins consist of several structural

domain. Ex. Protein pyruvate kinase show

three domains:

a) It contains an all- nucleotide binding

domain (in blue).

b) /-substrate binding domain (in grey).

c) /-regulatory domain (in green) connected

by several polypeptide linkers.

Wikipedia
Quaternary Structure of Proteins

Quaternary Structure: Polypeptide Chains Can Assemble

Into Multi-subunit Structures

? This level of protein structure applies only to those proteins that consist of more

than one polypeptide chain, termed subunits.

? Quaternary structure implies the non-covalent interaction that stabilise the

folded polypeptides leads to multisubunit proteins.
Cont--

? Multisubunit proteins can have a number of identical (homomeric) or non-

identical (heteromeric) subunits.

? The simplest multisubunit proteins are homodimers ? two identical polypeptide

chains that are independently folded but held together by non-covalent

interactions.

Cont--

? Example. Hemoglobin (Hb), oxygen

carrying protein in blood contains

four polypeptide chains and four

heme prosthetic groups, in which

the iron atoms are in the ferrous

(Fe2+) state.

? The protein portion, called globin,

consists of two -chains and two

-chains.

Fig.3.49: Biochemistry 7th edition by Berg, Tymoczko and Stryer
Cont--

? Subunits of Hb are arranged in symmetric pairs, each pair having one and one

subunit.

? Hb exists as an

2 2 tetramer. Subtle changes in the arrangement of subunits

within the Hb molecule allow it to carry oxygen from the lungs to tissues with

great efficiency.

Summary

? The gene-encoded primary structure of a polypeptide is the sequence of its

amino acids.

? Secondary structure refers to stable arrangements of amino acid residues giving

rise to recurring structural patterns.

? Folding of polypeptides into hydrogen-bonded motifs such as the helix, the -

pleated sheet, bends, and loops.
? Tertiary structure is the complete three-dimensional structure of a polypeptide

chain.

? When a protein has two or more polypeptide subunits, their arrangement in

space is referred to as quaternary structure

Interaction with students

? Distributed subtopics of class to students for participate in group

discussion in next class.
Reference Books

1) Harper 's Il ustrated Biochemistry-30th edition
2) Biochemistry. 4th edition. Donald Voet and Judith G. Voet.
3) Biochemistry 7th edition by Jeremy M. Berg, John L. Tymoczko and Lubert Stryer
4) Lehninger Principles of Biochemistry

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Thank you

This post was last modified on 05 April 2022