Essential Cell Biology 5th edition
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Essential Cell Biology 5th edition

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138 CHAPTER 4 Protein Structure and Functionamino acidside chains(A)unfolded proteinFOLDINGbinding sitefolded proteinHserineCCH 2O Nhydrogen bondH OCHHC5′ cyclic AMP bound toO O(CH 2 ) folded protein3NHP O+C NH O Oserine23′HarginineN N HOO CH CNH 2 2HHN H N NN HOH OC O_threonineelectrostaticattractionCHCH 2H 3 C CCH glutamicH2acidCH(B)Figure 4−32 Binding sites allow proteins to interact with specific ligands. (A) The folding of the polypeptidechain typically creates a crevice or cavity on the folded protein’s surface, where specific amino acid side chains arebrought together in such a way that they can form a set of noncovalent bonds only with certain ligands. (B) Close-upview of an actual binding site showing the hydrogen bonds and an electrostatic interaction formed between aprotein and its ligand (in this example, the bound ligand is cyclic AMP, shown in dark yellow).ECB5 04.32Although the atoms buried in the interior of a protein have no direct contactwith the ligand, they provide an essential framework that gives thesurface its contours and chemical properties. Even tiny changes to theamino acids in the interior of a protein can change the protein’s threedimensionalshape and destroy its function.Humans Produce Billions of Different Antibodies, Eachwith a Different Binding SiteAll proteins must bind to specific ligands to carry out their various functions.For antibodies, the universe of possible ligands is limitless andincludes molecules found on bacteria, viruses, and other agents ofinfection. How does the body manage to produce antibodies capable ofrecognizing and binding tightly to such a diverse collection of ligands?Antibodies are immunoglobulin proteins produced by the immune systemin response to foreign molecules, especially those on the surface ofan invading microorganism. Each antibody binds to a particular targetmolecule extremely tightly, either inactivating the target directly or markingit for destruction. An antibody recognizes its target molecule, calledan antigen, with remarkable specificity. And because there are potentiallybillions of different antigens we might encounter, humans must beable to produce billions of different antibodies—one of which will be specificfor almost any antigen imaginable.Antibodies are Y-shaped molecules with two identical antigen-bindingsites, each of which is complementary to a small portion of the surfaceof the antigen molecule. A detailed examination of antibody structurereveals that the antigen-binding sites are formed from several loopsof polypeptide chain that protrude from the ends of a pair of closely

How Proteins Work139antigenbindingsiteantigenSSV H domainSShypervariableloops thatbind antigenlight chainS SSSS SSSNH 2V L domainS SSSS SS SSSSSheavy chainSSSS5 nmSSSSvariable domainof light chain (V L )(A)HOOCdisulfidebond(B)constant domainof light chainFigure 4−33 An antibody is Y-shaped and has two identical antigen-binding sites, one on each arm of the Y.(A) Schematic drawing of a typical antibody molecule. The protein is composed of four polypeptide chains (twoidentical heavy chains and two identical, smaller light chains), stabilized and held together by disulfide bonds (red).Each chain is made up of several similar domains, here shaded with blue, for the variable domains, or gray, for theconstant domains. The antigen-binding ECB5 site e4.33-4.33 is formed where a heavy-chain variable domain (V H ) and a light-chainvariable domain (V L ) come close together. These are the domains that differ most in their amino acid sequence indifferent antibodies—hence their name. (B) Ribbon drawing of a single light chain showing that the most variableparts of the polypeptide chain (orange) extend as loops at one end of the variable domain (V L ) to form half of oneantigen-binding site of the antibody molecule shown in (A). Note that both the constant and variable domains arecomposed of a sandwich of two antiparallel β sheets connected by a disulfide bond (red).juxtaposed protein domains (Figure 4−33). The amino acid sequence inthese loops can vary greatly without altering the basic structure of theantibody. An enormous diversity of antigen-binding sites can thereforebe generated by changing only the length and amino acid sequence ofthese “hypervariable loops,” which is how the wide variety of differentantibodies is formed (Movie 4.7).With their unique combination of specificity and diversity, antibodies arenot only indispensable for fighting off infections, they are also invaluablein the laboratory, where they can be used to identify, purify, and studyother molecules (Panel 4−2, pp. 140–141).Enzymes Are Powerful and Highly Specific CatalystsFor many proteins, binding to another molecule is their main function.An actin molecule, for example, need only associate with other actinmolecules to form a filament. There are proteins, however, for whichligand binding is simply a necessary first step in their function. This is thecase for the large and very important class of proteins called enzymes.These remarkable molecules are responsible for nearly all of the chemicaltransformations that occur in cells. Enzymes bind to one or more ligands,called substrates, and convert them into chemically modified products,

How Proteins Work

139

antigenbinding

site

antigen

S

S

V H domain

S

S

hypervariable

loops that

bind antigen

light chain

S S

S

S

S S

S

S

NH 2

V L domain

S S

S

S

S S

S S

S

S

S

S

heavy chain

S

S

S

S

5 nm

S

S

S

S

variable domain

of light chain (V L )

(A)

HOOC

disulfide

bond

(B)

constant domain

of light chain

Figure 4−33 An antibody is Y-shaped and has two identical antigen-binding sites, one on each arm of the Y.

(A) Schematic drawing of a typical antibody molecule. The protein is composed of four polypeptide chains (two

identical heavy chains and two identical, smaller light chains), stabilized and held together by disulfide bonds (red).

Each chain is made up of several similar domains, here shaded with blue, for the variable domains, or gray, for the

constant domains. The antigen-binding ECB5 site e4.33-4.33 is formed where a heavy-chain variable domain (V H ) and a light-chain

variable domain (V L ) come close together. These are the domains that differ most in their amino acid sequence in

different antibodies—hence their name. (B) Ribbon drawing of a single light chain showing that the most variable

parts of the polypeptide chain (orange) extend as loops at one end of the variable domain (V L ) to form half of one

antigen-binding site of the antibody molecule shown in (A). Note that both the constant and variable domains are

composed of a sandwich of two antiparallel β sheets connected by a disulfide bond (red).

juxtaposed protein domains (Figure 4−33). The amino acid sequence in

these loops can vary greatly without altering the basic structure of the

antibody. An enormous diversity of antigen-binding sites can therefore

be generated by changing only the length and amino acid sequence of

these “hypervariable loops,” which is how the wide variety of different

antibodies is formed (Movie 4.7).

With their unique combination of specificity and diversity, antibodies are

not only indispensable for fighting off infections, they are also invaluable

in the laboratory, where they can be used to identify, purify, and study

other molecules (Panel 4−2, pp. 140–141).

Enzymes Are Powerful and Highly Specific Catalysts

For many proteins, binding to another molecule is their main function.

An actin molecule, for example, need only associate with other actin

molecules to form a filament. There are proteins, however, for which

ligand binding is simply a necessary first step in their function. This is the

case for the large and very important class of proteins called enzymes.

These remarkable molecules are responsible for nearly all of the chemical

transformations that occur in cells. Enzymes bind to one or more ligands,

called substrates, and convert them into chemically modified products,

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