Chapter 6 Flashcards
in 1934, J.D. Bernal and Dorothy Crowfoot Hodgkin showed that a crystal of the protein … yielded a discrete diffraction pattern when placed in an X-ray beam
pepsin
… is the local spatial arrangement of a polypeptide backbone atoms without regard to the conformations of its side chains
secondary structure
… refers to the three dimensional structure of an entire polypeptide including its side chains
tertiary
many proteins are composed of 2/more polypeptide chains, loosely referred to as … A protein’s … refers to the spatial arrangement of its subunits
subunits; quarternary
the … has a rigid, planar structure as a consequence of resonance interactions that give the peptide bond ~40% double-bond character
peptide group
the planar conformation of the peptide group maximizes …, which accounts for its rigidity
pi bonding overlap
peptide groups, with few exceptions, assume the … conformation, in which successive alpha C atoms are on opposite sides of the peptide bond joining them .
trans
Steric interference of cis conformation of peptide groups is reduced in peptide bonds to …, so ~10% of these residues in proteins follow a cis peptide bond
proline
the conformation of the backbone of a polypeptide chain can be described by the … angles (also called … angles or … angles) around the Calpha - N bond (…) and the Calpha- C bond (…) of each residue
torsion; dihedral; rotation; chi; psi
chi and psi angles are both … degrees with the polypeptide chian is in its fully extended conformation and increase .. when viewed from the alpha carbon
180; clockwise
sterically forbidden conformations have chi and psi values that would bring atoms closer than the corresponding … (the distance of closest contact between nonbonded atoms) –> this is the info summarized in a … diagram
van der Waals distance; Ramachandran
exceptions to the allowed regions of the Ramachandran plot:
cyclic side chain of Pro limits its range of chi values to angles of around -60 degrees, making it the most … amino acid residue
gly, without a beta C, is much less … than the other amino acid residues. Its permissible range of chi and psi covers a larger area of the diagram. at gly residues, polypeptide chains often assume conformations that are forbidden to other residues
conformationally restricted; sterically hindered
regular secondary structures: … and the …
alpha helix; beta sheet
only one polypeptide helix has both a favorable H-bonding pattern and chi and psi values that fall within the fully allowed regions of the Ramachandran diagram: the …
alpha helix
the alpha helix, which ideally has chi = -57 and psi = 047, has … residues per turn and a … (the distance the helix rises along its axis per turn) of 5.4 Angstroms
3.6; pitch
in the alpha helix, the backbone H bonds are arranged such that the peptide C = O bond of the nth residue points along the helix axis toward the peptide N-H of the … residue
(n + 4)th
like an alpha helix, the beta sheet uses the full H-bonding capacity of the polypeptide backbone. in b sheets, however, H-bonding occurs between … rather than within one
neighboring polypeptide chains
beta sheets in proteins contain 2 to as many as 22 polypeptide strands, with an average of … strands. each strand may contain up to … residues, the avg being .. residues
6; 15; 6
parallel beta sheets containing fewer than .. strands are rare, which suggests that parallel beta sheets are less … than antiparallel beta sheets, possibly because the H-bonds of parallel sheets are distorted compared to those of the antiparallel sheets
five; stable
beta sheets exhibit a pronounced … handed twist when viewed along their polypeptide strands. conformational energy calcs indicate that the twist is a consequence of interactions between chiral L-amino acid residues in the extended polypeptide chains. the twist distorts and weakens the beta sheet’s interchain …
right; H-bonds
… = connectivity
topology
polypeptide segments with regular secondary structure, such as alpha helices/strands of beta sheets, are often joined by stretches of polypeptide that abruptly change direction. such … or … (so named bc they often connect successive strands of antiparallel beta sheets) almost always occur at protein surfaces
reverse turns; beta bends
reverse turns/ beta bends usually involve four successive amino acid residues arranged in one of two ways, .. and …, that differ by a 180 degree flip of the peptide unit linking residues 2 and 3. both types of turns are stabilized by a …
type I and type 2; hydrogen bond
in type II for reverse turns, the oxygen atom of residue 2 crowds the beta carbon of residue 3, which is therefore usually … residue 2 of either type of turn is often …, since it can assume the required conformation
glycine; proline
proteins have historically been classified as either … or …
fibrous; globular
… is a protein that is the principal component of vertebrates’ outer epidermal layer and its related appendages, such as hair, horn, nails , and feathers
keratin
keratins have been classified as either … keratins, which occur in mammals, or … keratins, which occur in birds and reptiles. humans have more than 50 keratin genes expressed in a tissue-specific manner
alpha; beta
two alpha keratin polypeptides, each of which forms an …, twist around each other to form a … coil. the assembly is said to have a … structure because each alpha helix itself follows a helical path
alpha helix; left handed; coiled coil
alpha keratin is rich in … residues, which form disulfide bonds that cross link adjacent polypeptide chains. alpha keratins are classified as hard or soft according to whether they have a high or low … content
cys; sulfure
the springiness of hair and wool fibers is a consequence of the coiled coil’s tendency to … after being untwisted by stretching
recover its original conformation
collagen is the most abundant vertebrate protein. a single collagen molecule consists of … polypeptide chains.
three
collagen has a distinctive amino acid composition: nearly one third of its residues are …; another 15 to 30% of its residues are Pro and….
… and …. residues also occur, but in smaller amounts
Gly; 4-hydroxyprolyl (hyp)
3- hydroxyprolyl; 5-hydroxylysyl (hyl)
pro residues in collagen are converted to hyp in a reaction catalyzed by … this enzyme requires … to maintain its activity
prolyl hydroxylase; ascorbic acid (vitamin C)
the amino acid sequence of a typical collagen polypeptide consists of monotonously repeating triplets of sequence ..-…-… over a segment of about 1000 residues, where X is often … and Y is often …
… sometimes appears at the Y position
Gly-X-Y; Pro; Hyp; Hyl
the collagen polypeptide assumes a … handed helical conformation with about … residues per turn. three parallel chains wind around each other with a gentle, right-handed, ropelike twist to form the triple-helical structure of a collagen molecule
left; three
the crowding of the conformation of collagen explains the absolute requirement for a gly at every .. position of a collagen polypeptide chian. the three polypeptide chains are staggered so that a …, …, and … residue occurs at each level along the triple helix axis
third; Gly-X-Y;
collagen is covalently …, which accounts for its poor solubility. up to four lys, hyl, and his side chains are covalently cross linked to form compounds such as ….
cross linked; histidinodehydrohydroxymerodesmosine
… an enzyme that converts lys residues to those of the aldehyde allysine
lysyl oxidase
in collagen, the cross links do not form at random, but tend to occur near the … and … of the collagen molecules. the degree of cross linking in a particular tissue increases with age, which is why meat from older animals is tougher than from younger
N- and C- termini
segments of polypeptide chains whose successive residues do not have similar chi and psi values are sometimes called …
coils
…: the totally disordered and rapidly fluctuating conformations assumed by denatured proteins in solution
random coil
in … (folded) proteins, nonrepetitive structures are no less ordered than are helices or beta sheets; they are simply irregular and hence more difficult to describe
native
variations in amino acid sequence, as well as the overall structure of the folded proteins, can distort the … of secondary structural elements. for example, the alpha helix frequently deviates fromt he ideal conformation in the initial and final turns of the helix. similarly, a strand of polypeptide in a beta sheet may contain an extra residue that is not hydrogen bonded to a neighboring strand, producing a distortion known as a ..
regular conformations; beta ulge
many of the limits on amino acid composition and sequence may be due in part to … in the three dimensional structure of proteins
conformational constraints
the presence of certain residues outside of alpha helices or beta sheets may also be nonrandom. for example, alpha helices are often flanked by residues such as Asn and Gln, whose side chains can fold backto form H bonds with one of the four terminal residues of the helix, a phenomenon termed ..
helix capping
… is a technique that directly images molecules. a crusytal of the molecule to be imaged is exposed to a collimated beam of X rays and the resulting …, which arises from the regularly repeating positions of atoms in the crystal, is recorded by a radiation detector or on photographic film;
x-ray crystallography ; diffraction pattern
… particle accelerators that produce x rays of far greater intensity
synchrotrons
an x ray structure is an image of the … of the object under study. these maps are usually presented with the aid of computer graphics as one or more sets of .., in which acontour represents a specific level of electron density
electron density; contours
protein crystals are typically 40 to 60% … by volume
water
for electron density maps, side chains of comparable size and shape cannot always be differentiated. consequently, a protein structure cannot be elucidated from its electron density map alone, but knowing the … of the protein permits the sequence of amino acid residues to be fitted to the map
primary structure
crystalline proteins assume very nearly the same structures they have in … a protein molecule in a crystal is essentially in solution bc it is bathed by solvent of crystallization over all of its surface except for the few, generally small, patches that contact neighboring protein molecules
solution
crystal packing forces do not greatly perturb the … of protein molecules
structures
a proteins conventional 1D proton NMR is crowded with overlapping peaks, a problem addressed by … NMR, which yields additional peaks arising from the interactions of protons less than 5 angstroms appart
2D
interatomic distance measurements btwn identified paris of atoms, together with known geometric constraints such as covalent bond distances and angles, group planarity, chirality, and van der waals radii, are sued to compute the protein’s … these results, though, are consistent with an ensemble of closely related structures
3D structure
…: a hydrated sample is cooled to near liquid nitrogen temperatures so rapidly that the water in the sample does not have time to crystallize but rather assumes a vitreous (glasslike) state, allowing the protein sample to reamin hydrated and retain its native structure
cryo electron microscopy
cryo-EM holds great promise for determining the structures of fragile/flexible complexes that are difficult to … and too … to visualize by NMR
crystallize; large
the primary structures of globular proteins generally lack the repeating sequences that support the regular conformations seen in fibrous proteins. however, the amino acid side chains in globular proteins are spatially distributed according to their …
polarities
the uncharged polar groups are usually on the protein … but also occur in the .. of the molecule. when buried in the protein, these residues are almost always H bonded to other groups; in a sense, the formation of an H bond .. their polarity
surface; interior; neutralizes
turns and loops joining secondary structural elements usually occur at the …
protein surface
… or …: groupings of secondary structural elements
supersecondary structures; motifs
…: an alpha helix connects two parallel strands of a beta sheet
beta-alpha-beta motif
… motif: antiparallel strands connected by relatively tight reverse turns
beta hairpin motif
…: two successive antiparallel alpha helices pack against each other with their axes inclined. this permits energetically favorable intermeshing of their contacting side chains. similar associations stabilize the coiled coil conformation of alpha keratin and tropomyosin
alpha-alpha motif
…: a beta hairpin is folded over to form a 4 stranded antiparallel beta sheet
greek key motif
some proteins, such as e. coli cytochrome b562, consist only of alpha helices spanned by short connecting links and are therefore classified as …
alpha proteins
others, such as immunoglobulins, which contain the …, are called .. proteins because they have a large proportion of beta sheets and are devoid of alpha helices
immunoglobulin fold; beta
most proteins, including lactate dehydrogenase and carboxypeptidase A are known as … proteins bc they largely consist of mixtures of both types of secondary structure
alpha/beta proteins
the alpha, beta, and alpha/beta classes can be further categorized according to their …: that is, according to how their secondary structural elements are connected. for example, extended beta sheets often roll up to form …
topology; beta barrels
…: can be considered as a set of overlapping beta-alpha-beta motifs (member of the alpha/beta class of proteins)
alpha/beta barrel
polypeptide chains containing more than 200 residues usually fold into 2/more globular clusters known as .., which give these proteins a bi- or multilobal appearance. for example, each subunit of glyceraldehyde 3-phosphate dehydrogenase has 2 domains
domains
domains each consist of two or more layers of … this is bc at least two such layers are required to seal off a domains’s … from its aqueous environment
secondary structural elements; hydrophobic core
many domains are … units that have the characteristics of small globular proteins
structurally independent
the … is the fundamental unit of protein evolution
domain
the most common protein domains are evolutionary sinks– domains that arose and persisted bc of their ability to form …, to tolerate amino acid deletions, substitutions, and insertions, and/or to support essential …
stable folding patterns; biological functions
the essential … and …. elements of proteins, rather than their amino acid residues, are conserved during evolution
structural; functional
… is the rapidly growing discipline that deals with the burgeoning amount of information related to molecular sequences and strcutrues
bioinformatics
… is a branch of bioinformatics that is concerned with how macromolecular structures are displayed and compared
structural bioinformatics
most proteins are structurally related to other proteins, as evolution tends to conserve the … of proteins rather than their …
structures; sequences
increasing the size of an enzyme through the association of … is more efficient than increasing the length of its polypeptide chain because each subunit has an … more importantly, the subunit construction of many enzymes provides the structural basis for the … of their activities
identical subunits; active site; regulation
proteins with more than one subunit are called …, and their identical units are called …
oligomers; protomers
a protomer may consist of one polypeptide chain, or several unlike polypeptide chains. in this sense, hemoglobin is a dimer of ..
alpha beta protomers
the contact regions between subunits resemble the
interior of a single subunit protein
each protomer occupies a … position in the oligomer. proteins cannot have inversion/mirror symmetry, because bringing the protomers into coincidence would require converting chiral L residues to D residues. thus, proteins can only have …..
geometrically equivalent; rotational symmetry
…: simplest type of rotational symmetry in which protomers are related by a single axis of rotation
cyclic symmetry
…; more complicated type of rotational symmetry, generated when an n-fold rotation axis intersects a twofold rotation axis at right angles. an oligomer with Dn (dihedral) symmetry consists of … promoters. … symmetry is the most common type of dihedral symmetry in proteins
dihedral symmetry; 2n; D2
native proteins are only … under physiological conditions
marginally stable
the … is the major determinant of native protein structure
hydrophobic
the combined hydrophobic and hydrophilic tendencies of individual amino acid residues in proteins can be expressed as … the greater a side chain’s, the more likely it is to occupy the … of a protein
hypdropathies; interior
the factors that affect solubility are, in order the … of the substituted reside, its … compatibility, and, last, the … of its side chain
hydrophobicity; steric; volume
hydrogen bonds, which are central features of protein structures, make only minor contributions to … this is bc h bonding groups in an unfolded protein form h bonds with water molecules
protein stability
the association of two ionic protein groups of opposite charge is known as an … or a … these interactions contribute little to the stability of a native protein bc the free energy of the charge-charge interactions usually fails to compensate for the loss of entropy of the side chains
ion pair; salt bridge
disulfide bond are not essential stabilizing forces. they may be important for … a particular backbone folding pattern as the protein proceeds from its fully extended state to its mature form. these bonds are rare in intracellular proteins bc the cytoplasm is a … enviro
locking in ; reducing
metal ions may function to internally cross link proteins. for example, … hve been described, which contain residues arranged around Zn2+ ions tetrahedrally coordinated by the side chains of cys, his, and occasionally asp or glu
zinc fingers
proteins can be denatured reversibly. … is one of these proteins that can renature spontaneously
ribonuclease A (RNase A)
Anfinsen’s work with RNase A demonstrated that proteins can fold … into their native conformations under … conditions. this implies that a protein’s … dictates its 3D structure
spontaneously; physiological; primary structure
proteins are … and rapidly … molecules whose structural mobilities are functionally significant
flexible; fluctuating
conformational flexibility, or …, with structural displacement of up to 2 angstroms, allows small molecules to diffuse in and out of the interior of certain proteins. in some cases, a proteins’ conformational flexibility includes two stable alternatives in dynamic equilibrium. a change in cellular conditions, or the presence of a binding partner can tip the balance toward one conformation or the other
breathing
an entire protein/ long polypeptide segment may lack defined structure in its native state. such … proteins are characterized by sequences rich in certain polar and charged amino acids and lacking in bulky hydrophobic groups
intrinsically disordered;
in general, intrinsically disordered proteins tend to participate in … and …, whereas ordered proteins are involved largely in … rxns, … processes, and … functions
signaling; regulation; catalytic; transport; structural
intrinsically disordered proteins often adopt a specific secondary/tertiary structure when they bind to other things. for example, the transcription factor … is disordered when free in solution but folds to an ordered conformation when it interacts with the CREB-binding protein
CREB (cyclic AMP response element-binding protein)
studies of protein stability and renaturation suggest that protein folding is directed largely by the residues that occupy the … of the folded protein
interior
proteins fold to their native conformations via … rather than stumbling on them through random conformational searches
directed pathways
protein folding begins with the formation o f… of secondary segments
local segments
because native proteins contain compact hydrophobic cores, it is likely that the driving force in protein folding is what has been termed a … the collapsed state is known as a …, a species that has much of the secondary structure of the native protein but little of its tertiary structure
hydrophobic collapse; molten globule
the secondary structure becomes stabilized and tertriary structure begins to form. during this intermediate stage, the nativelike elements are thought to take the form of … that are not yet properly docked to form domains. in the final stage of folding the protein undergoes a series of complex rearrangements
subdomains
proteins appear to fold in a … manner, with small local elements of structure forming and then coalescing to yield larger elements, which coalesce with other such elements to form yet larger elements, etc
hierarchical
a folding protein must proceed from a high …, high … state to a low …, low … state. this energy entropy relationship is diagrammed in a …
energy; entropy; energy; entropy; folding funnel
proteins have evolved to have … as well as stable native conformations
efficient folding pathways
…. catalyzes the process of disulfide interchange through which proteins form native disfulfide bonds
protein disulfide isomerase (PDI)
… are essential proteins that bind to unfolded and partially folded polypeptide chains to disrupt the improper association of exposed hydrophobic segments that would otherwise lead to non-native folding as well as polypeptide aggregation and precipitation
molecular chaperones
many molecular chaperones were first described as … bc their rate of synthesis is increased at elevated temps
heat shock proteins
the …, in association with the cochaperone Hsp40, facilitate the folding of newly synthesized proteins and reverse the denaturation and aggregation of proteins. they also function to unfold proteins in preparation for their transport through membranes and to subsequently refold them
Hsp70
…: ribosome associated chaperone in prokaryotes that prevent aggregation of polypeptides as they emerge from the ribosome
trigger factor
the … form large multisubunit, cagelike assemblies in both prokaryotes and eukaryotes. they bind improperly folded proteins and induce them to refold inside an internal cavity
chaperonins
the …, mainly facilitate the late stages of folding of proteins involved in cellular signaling. among the most abundant proteins in eukaryotes
hsp90
most molecular chaperones are …; that is, enzymes that catalyze the hydrolysis of atp to adp and inorganic phosphate
ATPases
the chaperonins in e. coli consist of two types of subunits named … and …
GroEL and GroES
diseases caused by protein misfolding include the …, …, …, and the … all of which may be transmitted by prions
amyloidosis; alzheimers; Parkinson’s; transmissible spongiform encephalopathies (TSEs)
the misfolded proteins form fibrils containing extensive … structure
beta
