8/8/2019 Structure of Ig

1/18

IMMUNOGLOBULIN

By : Lisa Nathalie

MSc. Biotechnology 1st Semester

November 27th, 2010

lisa_nathalie@yahoo.com

8/8/2019 Structure of Ig

2/18

Introduction

Ig / Antibody is a glycoprotein polypeptide and

carbohydrate

Polypeptide 2 identical light (L) chains (22,000 Da) + 2identical heavy (H) chains (55,000 Da)

Each LC is bound to a HC by a disulfide bond and by non

covalent interx. (salt linkages, hydrogen bonds, and

hydrophobic interx.) to form a heterodimer (H-L) The carbohydrate region lies in between particular part

of heavy chain, i.e. CH2

8/8/2019 Structure of Ig

3/18

Structure of Ig

VRCDR,binds to Ag

Fd : HCportion of Fab (VH-

CH1)

Fv : var. of Fab (VH-VL)

Fb : Const. of Fab: (CH1-CL

(Paul, 2008)

8/8/2019 Structure of Ig

4/18

Continue Structure of Ig

Heavy chains :

5 isotypes of the constant region : , ,

, , and with the corresponding

subclasses, IgA, IgD, IgE, IgG, and IgM,

respectively.Light chains :

The constant region had 1-2 aa

sequences and light chain

Human 60% , 40 %

Mice 95% , 5 %

In normal Ig molecule : either or ,

never both

8/8/2019 Structure of Ig

5/18

Chemical and enzymatic methods

involved in antibody structure

(Kindt et al., 2006)

8/8/2019 Structure of Ig

6/18

Hinge Region

It is an extended peptide sequence between

CH1 and CH2 domains on IgG, IgD, and IgA that

has no homology with other domains

Proline and cysteine residues are predominant

Proline flexibility to Fab arms to respond

when antigen is bound

Cysteine form interchain disulfide bonds

that hold the two heavy chains together

8/8/2019 Structure of Ig

7/18

Structure Organization

PRIMARY STRUCTURE

the sequence of amino acids consist of the V and C

regions of the light and heavy chain

SECONDARY STRUCTURE

Folding of the extended polypeptide chain upon itself

into a series of antiparallel pleated sheets

(Kindt et al., 2006)

8/8/2019 Structure of Ig

8/18

Continue structure organization

(Kindt et al., 2006)

Secondary structure

8/8/2019 Structure of Ig

9/18

Continue Structure Organization

TERTIARY STRUCTURE

in compact globular domains which are connected to

neighboring domains by stretches of the polypeptidechain between regions of pleated sheet.

QUATERNARY STRUCTURE

The globular domains of adjacent heavy and lightpolypeptide chains interact in the quaternarystructure, forming functional domains biologicaleffectors functions and specific Ag binding

8/8/2019 Structure of Ig

10/18

Continue structure organization

(Kindt et al., 2006)

Quaternary structure

8/8/2019 Structure of Ig

11/18

IgG

Most abundant 80% of the total serum Ig

Human IgG subclasses : IgG1, IgG2, IgG3, and IgG4

(difference in -chain constant-region sequence and are

numbered according their decreasing average-serumconcentr.)

Structure differs in hinge region and the number an the

position of the interchain disulfide bonds between the

heavy chains

(Kindt et al., 2006)

8/8/2019 Structure of Ig

12/18

IgM

1st Ig to be synthesized by neonatesand the 1st Ig class produced inresponse to an Ag

Pentamer 5 monomers are holdtogether by disulfide bonds that linktheir carboxyl-terminal C4/ C4 and

their C3/ C3 domains J (joining) chain : extended

polypeptide, disulfide-bonded to thec-terminal cysteine residue of two ofthe 10 chains, polymerization ofthe monomers to form pentamericIgM.

Pentameric structure 10 Ag bindingsites

Steric hindrance five or fewermolecules of larger Ag can be boundsimultaneously

8/8/2019 Structure of Ig

13/18

IgA

Predominant in external secretions, such asbreast, milk, saliva, tears, and mucus ofbronchial, genitourinary, and digestive tracts.

In serum monomer, but polymeric forms(dimmers, trimers, and some tetramers) aresometimes seen, all containing J-chainpolypeptide

SecIgA cross-link large antigens (Ag) withmultiple epitopes (the region on antigen onwhich is bound to Ig) prevents the attachmentof the pathogens to the mucosal cells, thusinhibits the infection

Secretory IgA in breast milk protect thenewborn babies against infection during the firstmonth of life

8/8/2019 Structure of Ig

14/18

IgD and IgE

Ig D

Biological marker of mature

B cells, fx. not yet identified

IgE

binds to the Fc receptors on

blood basophils and tissue

mast cells membranes

allergic reactions

8/8/2019 Structure of Ig

15/18

Properties of Human Igs

8/8/2019 Structure of Ig

16/18

Properties of Human Igs (continued)

8/8/2019 Structure of Ig

17/18

Other Types of Ig

IgT in teleost fish

IgZ in zebrafish

IgY in chicken, birds, reptiles, amphibian, andChinese soft-shelled turtle (Pelodiscus

sinensis)

8/8/2019 Structure of Ig

18/18

Reference :

- Kindt, T.J., Osborne, B.A., and Goldsby, R.A., 2006.

Kuby Immunology, 6th edition. WH Freeman.

- Paul, W.E., 2008. Fundamental Immunology, 6th ed.

Washington D.C.: Lippincott Williams and Wilkins.