4. protein functions

8/13/2019 4. Protein Functions

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Proteins can be classified intotwo broad types:

Active proteins - enzymes , the biological catalysts that make possible the

thousands of chemical reactions that go on inside a living cell.- microtubule proteins that produce movement in the cell

- membrane-bound proteins that regulate pumping of ions andnutrients across the membrane.

Structural proteins- contribute to the structural properties of the cell and the

organism; human hair keratin and bone collagen are two structuralproteins.

Some proteins are both active and structural, for example, thecontractile proteins actin and myosin , which comprise the great bulk of

muscles and hence affect shape.


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Enzyme Function Active sites

Enzymes are biological catalysts that speed up chemicalreactions that otherwise would occur too slowly for cellsto function.

The substrate molecules fit into an enzyme's active site.

Enzymes do their job of catalysis by physically grapplingwith the substrate molecules, interacting with them tomake or break chemical bonds.


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Schematic representation of the action of a hypotheticalenzyme in putting two substrate molecules together

(a) In the "lock-and-key"mechanism the substrateshave a complementary fit to theenzyme's active site.

(b) In the induced-fit model,binding of substrates induces aconformational change in theenzyme.

(c) Enzymes are highly specific forthe chemical reactions theycatalyze, and the specificity liesin the precise fit betweensubstrate and active site.


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Malfunctioning Alleles

In genetics the standard organismal phenotype is calledthe wild-type, because this is the type observed in thewild, in other words, in nature.

All essential genes must be capable of producing theirfunctional products in order to produce this wild-typephenotype.These normally functioning alleles are called wild-typealleles.


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Mutations (changes in the DNA sequence of a gene, occurspontaneously in nature).

Since alleles are forms of genes, mutations by definition create newalleles.In genetic research, a gene is generally symbolized by a letter or

several letters based on the word describing the phenotypeproduced by a mutant allele.Then the corresponding wild-type allele is designated by theaddition of a superscript plus sign (+).For example the wild-type eye color of the fruit fly Drosophila is red,

but a mutant allele of a gene on the X-chromosome produces whiteeyes, so the mutant allele is designated w and its wild-type allele isw +.


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Genetic disease

A common cause of genetic disease in humans isenzyme deficiency caused by mutation.Human cells carry two chromosome sets, so all genesare represented twice (gene pairs). Normally both arewild-type alleles.However, individuals carrying a pair of defective allelesof a gene coding for an enzyme will show reduced or noenzyme activity and express disease symptoms.


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Mutations can lead to gene malfunction by changesin sequences that are protein-coding or importantfor information processing.


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Gene Mutation

MISSENSE MUTATION In this example, the nucleotide adenine is replaced by cytosine inthe genetic code, introducing an incorrect amino acid into the

protein sequence.


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Gene Mutation

NONSENSE MUTATIONIn this example, the nucleotide cytosine is replaced by thymine inthe DNA code, signaling the cell to shorten the protein.


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Gene Mutation

INSERTION MUTATIONIn this example, one nucleotide (adenine) is added in the DNA code,changing the amino acid sequence that follows.


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Gene Mutation

DELETION MUTATIONIn this example, one nucleotide (adenine) is deleted from the DNAcode, changing the amino acid sequence that follows.


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Gene Mutation

FRAMESHIFT MUTATION A frameshift mutation changes the amino acid sequence from thesite of the mutation.


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Gene Mutation

REPEAT EXPANSION MUTATIONIn this example, a repeated trinucleotide sequence (CAG) adds aseries of the amino acid glutamine to the resulting protein.


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Effects of mutations on cellular function

Generally, mutations result in reduced protein function orno protein function.

A mutation with reduced function is called a leakymutation because some of the wild-type function "leaks"through into the phenotype.

A mutation that results in no protein function is called anull mutation.Changes that do not affect the function of a protein arecalled silent mutations.


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Positions of mutant sites and their functionalconsequences

Some mutations alter the information-transfer process rather than directly alteringthe genetic code.Some mutations produce malfunction notthrough any effect on amino acid sequencebut on intron splicing. Since intron splicingdepends on specific nucleotide sequencesat the exon-intron boundaries and insidethe intron, if these sites are mutated, theintron cannot be excised and no functional

mRNA will be produced.

A similar mutation alters the regulation of the gene. For example, the promotersequence to which the RNA polymerase binds is crucial, and if changes occur inthis sequence, the gene might not be transcribed at all or might be transcribed atabnormally low (or high) rates.


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Enzyme Failures. One small part of the human metabolic map, showing theconsequences of various specific enzyme failures.

(After I. M. Lerner and W. J. Libby, Heredity, Evolution, and Society, 2d ed. Copyright 1976 by W. H. Freeman andCompany.)


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Phenylketonuria (PKU)

A defect in the enzyme phenylalanine hydroxylasecauses a buildup of phenylalanine (originating fromdietary protein).

At high concentrations phenylalanine is converted intophenylpyruvic acid, a substance that interferes with thedevelopment of the nervous system, giving rise tomental retardation in an infant with two copies of thedefective allele.If the high level of phenylpyruvic acid is detected soonafter birth, the baby can be placed on a special low-phenylalanine diet and develops without retardation.


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Cystic Fibrosis

The mostcommonly foundmutation is a

deletion of threenucleotides, whichshould result in theremoval of the

amino acidphenylalanine fromthe primarysequence of theprotein.

The location of the cystic fibrosis gene on chromosome 7, with an enlargement showing the natureof the common 3-bp deletion that removes a phenylalanine from the polypeptide sequence.


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Cystic Fibrosis

This is not caused byan enzyme deficiencybut by inactivity of aprotein that controlsthe passage of chlorideions throughmembranes in

secretory tissue.

4. protein functions

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