8885ac05157-1898/12/038:55 AM Page163mac78mac78:385p Mb Hba Hb Mb Hbo HbB about one-third of the oxygen it carries, or 6.5 mL of O gas at atmospheric pressure and body temperature E D E Myoglobin, with its hyperbolic binding curve for oxygen (Fig. 5-4b), is relatively insensitive to small changes in the concentration of dissolved oxygen and LLL so functions well as an oxygen-storage protein. Hemo- globin, with its multiple subunits and O2-binding sites is better suited to oxygen transport. As we shall see, in- teractions between the subunits of a multimeric protein can permit a highly sensitive response to small changes GKvGAHAGEYGAEA LHcDKLHv in ligand concentration Interactions among the subunits in hemoglobin cause conformational changes that alter the affinity of the protein for oxygen. The modulation of oxygen binding allows the Oe-transport protein to re- spond to changes in oxygen demand by tissues Hemoglobin Subunits Are Structurally Similar to Myoglobin Hemoglobin (Mr 64, 500; abbreviated Hb) is rou LGNvLvcvLAHH spherical, with a diameter of nearly 5.5 nm. It is a tetrameric protein containing four heme prosthetic groups, one associated with each polypeptide chain. Adult hemoglobin contains two types of globin, two c chains(141 residues each) and two B chains (146 EFTP residues each). Although fewer than half of the amino acid residues in the polypeptide sequences of the a and B subunits are identical, the three-dimensional struc tures of the two types of subunits are very similar. Fur thermore, their structures are very similar to that of -G myoglobin(Fig. 5-6), even though the amino acid se- bers of the globin family of proteins. The helix-naming HE+ quences of the three polypeptides are identical at only 27 positions(Fig. 5-7). All three polypeptides are mem- convention described for myoglobin is also applied to the hemoglobin polypeptides, except that the a subunit lacks the short D helix. The heme-binding pocket made up largely of the e and f helices H26--L--- T Heme FIGURE 5-7 The amino acid sequences of whale myoglobin and the a and B chains of human hemoglobin Dashed lines mark helix bound. aries. To align the sequences optimally, short gaps must be introduced into both Hb sequences where a few amino acids are present in the mpared sequences. With the exception of the missing D helix in Hba, this alignment permits the use of the helix lettering convention that emphasizes the common positioning of amino acid residues that are identical in all three structures(shaded). Residues shaded in pink are conserved in all known globins. Note that the common helix letter- and-number designation for amino acids does not necessarily corre- spond to a common position in the linear sequence of amino acids Myoglobin B subunit of in the polypeptides. For example, the distal His residue is His E7 all three structures, but corresponds to His4, HisB, and Hissin the linear sequences of Mb, Hba, and HbB, respectively. Nonhelical FIGURE 5-6 A comparison of the structures of myoglobin( PDB Id residues at the amino and carboxyl termini, beyond the first(A) and MBO)and the B subunit of hemoglobin(derived from PDB ID 1 HGA). last(H)a-helical segments, are labeled NA and HC, respectivelyabout one-third of the oxygen it carries, or 6.5 mL of O2 gas at atmospheric pressure and body temperature. Myoglobin, with its hyperbolic binding curve for oxygen (Fig. 5–4b), is relatively insensitive to small changes in the concentration of dissolved oxygen and so functions well as an oxygen-storage protein. Hemo￾globin, with its multiple subunits and O2-binding sites, is better suited to oxygen transport. As we shall see, in￾teractions between the subunits of a multimeric protein can permit a highly sensitive response to small changes in ligand concentration. Interactions among the subunits in hemoglobin cause conformational changes that alter the affinity of the protein for oxygen. The modulation of oxygen binding allows the O2-transport protein to re￾spond to changes in oxygen demand by tissues. Hemoglobin Subunits Are Structurally Similar to Myoglobin Hemoglobin (Mr 64,500; abbreviated Hb) is roughly spherical, with a diameter of nearly 5.5 nm. It is a tetrameric protein containing four heme prosthetic groups, one associated with each polypeptide chain. Adult hemoglobin contains two types of globin, two
chains (141 residues each) and two  chains (146 residues each). Although fewer than half of the amino acid residues in the polypeptide sequences of the
and  subunits are identical, the three-dimensional struc￾tures of the two types of subunits are very similar. Fur￾thermore, their structures are very similar to that of myoglobin (Fig. 5–6), even though the amino acid se￾quences of the three polypeptides are identical at only 27 positions (Fig. 5–7). All three polypeptides are mem￾bers of the globin family of proteins. The helix-naming convention described for myoglobin is also applied to the hemoglobin polypeptides, except that the
subunit lacks the short D helix. The heme-binding pocket is made up largely of the E and F helices. Heme group Myoglobin b subunit of hemoglobin FIGURE 5–6 A comparison of the structures of myoglobin (PDB ID 1MBO) and the  subunit of hemoglobin (derived from PDB ID 1HGA). L A T V L Mb Hb
Hb Mb Hb
Hb only b Hb V VV E —P LFF — —H A —D EKR L L E —A FLL S ST M—V I LL EPP K —M SSG GAE D7 A G G EHN E DE E1 S S N ACV WKK EAP I LL QTS DQK I LV L NA LVV HVC V V KKK VTV L KT KGA LLL HAA E7 HHH HAA V AL GGG SAH W WW VKK G19 R H H A GG TKK HL F K KK VVV PPG V VV LAL GAK A16 E G — TDG DEE AA— A A FFF D HN LLF H1 G T T V AV GTS APP A GD AND DAP GEE I AG AVV HYV E19 L V L QHQ G GG KAA GAA QAG KHH ASA DEE KVL ML Y I AA GDD NDQ L LL HDN KKK I EG HML AFV R RR EPK LLV L ML ANG EAA F FL EAT LSG KLV F1 L L F FVV B16 S S V KSA RSA C1 H F Y PAT KTN P PP L L DVA ETW ASS I LL T T QDE ATA L KQ SLL H21 A S H ETR F8 HHH KKK HC1 C7 K Y F F9 A A C YYY HC2 F FF T HD KRH HC3 DPE KKK E R HS HL L H26 L F FF KRH G K —G I VV Y HDD G1 P D D Q L LL I PP G KSS KVE D1 T H T YNN 1 1 1 20 20 20 40 40 40 60 60 60 80 80 80 100 100 100 120 120 120 140 140 140 141 146 153 A1 B1 NA1 H and Proximal His Distal His FIGURE 5–7 The amino acid sequences of whale myoglobin and the
and chains of human hemoglobin. Dashed lines mark helix bound￾aries. To align the sequences optimally, short gaps must be introduced into both Hb sequences where a few amino acids are present in the compared sequences. With the exception of the missing D helix in Hb
, this alignment permits the use of the helix lettering convention that emphasizes the common positioning of amino acid residues that are identical in all three structures (shaded). Residues shaded in pink are conserved in all known globins. Note that the common helix-letter￾and-number designation for amino acids does not necessarily corre￾spond to a common position in the linear sequence of amino acids in the polypeptides. For example, the distal His residue is His E7 in all three structures, but corresponds to His64, His58, and His63 in the linear sequences of Mb, Hb
, and Hb, respectively. Nonhelical residues at the amino and carboxyl termini, beyond the first (A) and last (H)
-helical segments, are labeled NA and HC, respectively. 8885d_c05_157-189 8/12/03 8:55 AM Page 163 mac78 mac78:385_REB: