B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 48
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(C) If the two bindingsites are disposed appropriately in relation to each other, the protein subunitsmay form a closed ring instead of a helix. (For an example of A, seeFigure 3–18; for an example of B, see Figure 3–21; for examples of C, seeFigures 5–14 and 14–31.)(A)freesubunitsassembledstructuresdimerbindingsite(B)site complementary to another region of the surface of the same molecule (Figure3–20).
An actin filament, for example, is a long helical structure produced frommany molecules of the protein actin (Figure 3–21). Actin is a globular protein thatis very abundant in eukaryotic cells, where it forms one of the major filament systems of the cytoskeleton (discussed in Chapter 16).We will encounter many helical structures in this book. Why is a helix such acommon structure in biology? As we have seen, biological structures are oftenformed by linking similar subunits into long, repetitive chains.
If all the subunitsare identical, the neighboring subunits in the chain can often fit together in onlyone way, adjusting their relative positions to minimize the free energy of the contact between them. As a result, each subunit is positioned in exactly the same wayin relation to the next, so that subunit 3 fits onto subunit 2 in the same way thatsubunit 2 fits onto subunit 1, and so on. Because it is very rare for subunits to joinup in a straight line, this arrangement generally results in a helix—a regular structure that resembles a spiral staircase, as illustrated in Figure 3–22.
Depending onthe twist of the staircase, a helix is said to be either right-handed or left-handed(see Figure 3–22E). Handedness is not affected by turning the helix upside down,but it is reversed if the helix is reflected in the mirror.The observation that helices occur commonly in biological structures holdstrue whether the subunits are small molecules linked together by covalent bonds(for example, the amino acids in an α helix) or large protein molecules that arelinked by noncovalent forces (for example, the actin molecules in actin filaments).This is not surprising. A helix is an unexceptional structure, and it is generatedsimply by placing many similar subunits next to each other, each in the samestrictly repeated relationship to the one before—that is, with a fixed rotation followed by a fixed translation along the helix axis, as in a spiral staircase.helixbindingsites(C)ringbindingsitesactin moleculeMBoC6 m3.24/3.20minus endMany Protein Molecules Have Elongated, Fibrous ShapesEnzymes tend to be globular proteins: even though many are large and complicated, with multiple subunits, most have an overall rounded shape.
In Figure 3–21,we saw that a globular protein can also associate to form long filaments. But thereare also functions that require each individual protein molecule to span a largedistance. These proteins generally have a relatively simple, elongated three-dimensional structure and are commonly referred to as fibrous proteins.One large family of intracellular fibrous proteins consists of α-keratin, introduced when we presented the α helix, and its relatives. Keratin filaments areextremely stable and are the main component in long-lived structures such ashair, horn, and nails. An α-keratin molecule is a dimer of two identical subunits,with the long α helices of each subunit forming a coiled-coil (see Figure 3–9).
Thecoiled-coil regions are capped at each end by globular domains containing binding sites. This enables this class of protein to assemble into ropelike intermediatefilaments—an important component of the cytoskeleton that creates the cell’sinternal structural framework (see Figure 16–67).Fibrous proteins are especially abundant outside the cell, where they are amain component of the gel-like extracellular matrix that helps to bind collectionsof cells together to form tissues. Cells secrete extracellular matrix proteins intotheir surroundings, where they often assemble into sheets or long fibrils.
Collagen is the most abundant of these proteins in animal tissues. A collagen moleculeconsists of three long polypeptide chains, each containing the nonpolar amino37 nmplus end(A)50 nm(B)Figure 3–21 Actin filaments.(A) Transmission electron micrographs ofnegatively stained actin filaments.
(B) Thehelical arrangement of actin molecules in anactin filament. (A, courtesy of Roger Craig.)MBoC6 m3.25/3.21THE SHAPE AND STRUCTURE OF PROTEINS125lefthandedFigure 3–22 Some properties of a helix.(A–D) A helix forms when a series ofsubunits bind to each other in a regularway. At the bottom, each of these helicesis viewed from directly above the helix andseen to have two (A), three (B), and six(C and D) subunits per helical turn. Notethat the helix in (D) has a wider paththan that in (C), but the same number ofsubunits per turn. (E) As discussed in thetext, a helix can be either right-handed orleft-handed.
As a reference, it is useful toremember that standard metal screws,which insert when turned clockwise, areright-handed. Note that a helix retains thesame handedness when it is turned upsidedown. (PDB code: 2DHB.)righthanded(E)(A)(B)(C)(D)acid glycine at every third position. This regular structure allows the chains towind around one another to generate a long regular triple helix (Figure 3–23A).MBoC6bindm3.26/3.22Many collagen molecules thento one another side-by-side and end-toend to create long overlapping arrays—thereby generating the extremely toughcollagen fibrils that give connective tissues their tensile strength, as described inChapter 19.Proteins Contain a Surprisingly Large Amount of IntrinsicallyDisordered Polypeptide ChainIt has been well known for a long time that, in complete contrast to collagen,another abundant protein in the extracellular matrix, elastin, is formed as a highlydisordered polypeptide.
This disorder is essential for elastin’s function. Its relatively loose and unstructured polypeptide chains are covalently cross-linked toelastic fiber50 nmshort section ofcollagen fibrilcollagenmolecule300 nm × 1.5 nmSTRETCH1.5 nmcollagentriplehelixRELAXsingle elastin moleculecross-link(A)(B)Figure 3–23 Collagen and elastin. (A) Collagen is a triple helix formed by three extended protein chains that wrap around one another (bottom).Many rodlike collagen molecules are cross-linked together in the extracellular space to form unextendable collagen fibrils (top) that have the tensilestrength of steel. The striping on the collagen fibril is caused by the regular repeating arrangement of the collagen molecules within the fibril.(B) Elastin polypeptide chains are cross-linked together in the extracellular space to form rubberlike, elastic fibers.
Each elastin molecule uncoils into amore extended conformation when the fiber is stretched and recoils spontaneously as soon as the stretching force is relaxed. The cross-linking in theextracellular space mentioned creates covalent linkages between lysine side chains, but the chemistry is different for collagen and elastin.MBoC6 m3.27/3.23126Chapter 3: Proteinsproduce a rubberlike, elastic meshwork that can be reversibly pulled from oneconformation to another, as illustrated in Figure 3–23B.
The elastic fibers thatresult enable skin and other tissues, such as arteries and lungs, to stretch andrecoil without tearing.Intrinsically disordered regions of proteins are frequent in nature, and theyhave important functions in the interior of cells. As we have already seen, proteinsoften have loops of polypeptide chain that protrude from the core region of a protein domain to bind other molecules.
Some of these loops remain largely unstructured until they bind to a target molecule, adopting a specific folded conformation only when this other molecule is bound. Many proteins were also known tohave intrinsically disordered tails at one or the other end of a structured domain(see, for example, the histones in Figure 4–24). But the extent of such disorderedstructure only became clear when genomes were sequenced. This allowed bioinformatic methods to be used to analyze the amino acid sequences that genesencode, searching for disordered regions based on their unusually low hydrophobicity and relatively high net charge.
Combining these results with other data, it isnow thought that perhaps a quarter of all eukaryotic proteins can adopt structuresthat are mostly disordered, fluctuating rapidly between many different conformations. Many such intrinsically disordered regions contain repeated sequences ofamino acids. What do these disordered regions do?Some known functions are illustrated in Figure 3–24. One predominant function is to form specific binding sites for other protein molecules that are of highspecificity, but readily altered by protein phosphorylation, protein dephosphorylation, or any of the other covalent modifications that are triggered by cell signaling events (Figure 3–24A and B).
We shall see, for example, that the eukaryoticRNA polymerase enzyme that produces mRNAs contains a long, unstructuredC-terminal tail that is covalently modified as its RNA synthesis proceeds, therebyattracting specific other proteins to the transcription complex at different times(see Figure 6–22). And this unstructured tail interacts with a different type of lowcomplexity domain when the RNA polymerase is recruited to the specific sites onthe DNA where it begins synthesis.As illustrated in Figure 3–24C, an unstructured region can also serve as a“tether” to hold two protein domains in close proximity to facilitate their interaction.
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