The relationship between coding sequences and function in haemoglobin

Eaton, William A.

doi:10.1038/284183a0

Cited by 106 publications

(22 citation statements)

References 26 publications

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“…The analysis of hemoglobin functions showed that the amino acid residues associated with the heme contacts are concentrated in the central modules (M2 ϩ M3) as illustrated in Fig. 1 (6). In 1980, by using a protease, Craik et al (7,8) isolated the central region of the ␤-subunit, which corresponds to the module M2 ϩ M3 and is coded by the central exon of the ␤-subunit.…”

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confidence: 99%

Structural and Functional Roles of Modules in Hemoglobin

Inaba

Wakasugi

Ishimori

et al. 1997

Journal of Biological Chemistry

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The ␣-and ␤-subunits of human hemoglobin consist of the modules M1, M2 ؉ M3, and M4, which correspond to the exons 1, 2, and 3, respectively (Go, M. (1981) Nature 291, 90 -92). To gain further insight into functional and structural significance of the modules, we designed two kinds of chimeric hemoglobin subunits (chimeric ␣␣␤-and ␤␤␣-subunits), in which the module M4 was replaced by the partner subunits. CD spectra in the far-UV region showed that the secondary structure of the chimeric ␣␣␤-subunit drastically collapsed, while the chimeric ␤␤␣-subunit conserved the native globin structure (Wakasugi, K., Ishimori, K., Imai, K., Wada, Y., and Morishima, I. (1994) J. Biol. Chem. 269, 18750 -18756). SAXS data also suggested a partially disordered structure of the chimeric ␣␣␤-subunit. Based on tryptophan fluorescence spectra and computer modeling from x-ray structures of native globins, steric constraint between Trp 14 and Tyr 125 would be induced in the chimeric ␣␣␤-subunit, which would perturb the packing of the A-and H-helices and destabilize the globule structure. On the other hand, such a steric constraint was not found for the counterpart chimeric subunit, the ␤␤␣-subunit. The different stabilities of these module-substituted globins imply that modules would not always be stable "structural" units, and interactions between modules are crucial to construct stable globin subunits.Recent structural studies on proteins have revealed that some are constructed by "modules," which are compact structural units (1, 3). The exon shuffling in protein evolution with the correspondence of the module to the exon on the gene structure strongly suggested that the module structure is one of the key factors in evolution of structure and function of protein (4, 5). The module structure was first identified in the globin family (1), and their diagonal plots have clearly shown that both of the Hb subunits (␣-and ␤-subunits) consist of the four modular structures, the modules M1, M2, M3, and M4 (1), each of which is coded by an exon with the exception of the large central exon comprising two compact units.The analysis of hemoglobin functions showed that the amino acid residues associated with the heme contacts are concentrated in the central modules (M2 ϩ M3) as illustrated in Fig. 1 (6). In 1980, by using a protease, Craik et al. (7,8) isolated the central region of the ␤-subunit, which corresponds to the module M2 ϩ M3 and is coded by the central exon of the ␤-subunit. They showed that the fragment from the central region bound heme stoichiometrically and tightly, generating a characteristic strong Soret absorption band as found for the intact subunits. De Sanctis et al. (9 -12) also prepared "minimyoglobin," which is constructed by the peptide fragment from 32 (Leu) to 139 (Asn) of horse heart myoglobin. The heme binding property of the minimyoglobin peptide was almost the same as that of the intact myoglobin, and the heme binding induced the recovery of secondary structure of the minimyoglobin. They concluded that the remova...

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confidence: 99%

Structural and Functional Roles of Modules in Hemoglobin

Inaba

Wakasugi

Ishimori

et al. 1997

Journal of Biological Chemistry

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“…An original approach to investigate these fundamental aspects of protein structure and dynamics is to see if the domain encoded by the central exon of the myoglobin (Mb) gene, which consists of three exons and two long introns (3), behaves dynamically like the parent protein or if it displays peculiar properties. An answer to this question is also necessary to better understand why there are three exons in the genes encoding Mb and the hemoglobin (Hb) chains (4)(5)(6)(7).…”

Section: Tionmentioning

confidence: 99%

“…Given the similarity in the three-dimensional folding of Mb and Hb subunits (11) and in the exon-intron structure of the genes encoding for these proteins, 11 mini-Mb serves as a model ofgeneral validity. The central exons ofthe Mb and Hb chain genes code for the domain that provides the hydrophobic crevice where heme is bound, and the role proposed for the C-and N-terminal fragments is to optimize the fit between crevice and prosthetic group (6,7,12).…”

Section: Tionmentioning

confidence: 99%

Protein dynamics in minimyoglobin: is the central core of myoglobin the conformational domain?

Iorio

Calonder

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The kinetics of CO binding to the horse myoglobin fragment Mb-(32-139), the so-called "mini-Mb," were investigated by laser flash photolysis in 0.1 M phosphate buffer and in buffer with 75% (vol/vol) glycerol. The reaction displays complex time courses that can be approximated satisfactorily only with a sum of five exponentials. The features of the kinetic components and a comparison of the deoxy-minuscarbonyl difference spectra of mini-Mb and horse Mb obtained under equilibrium conditions, with the kinetic difference spectra resulting from the global analysis of the traces recorded between 400 and 450 nm, show that CO binding to mini-Mb is accompanied by large structural changes. In view of the fact that mini-Mb is an approximation ofthe Mb-(31-105) fragment encoded by the central exon of the Mb gene, this finding is particularly relevant. On the basis of our data and previous reports

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“…They do, however, correspond to smaller, compact "modules" on the basis of a-carbon distance analysis (10). The central exon encodes a module that binds heme tightly and specifically but does not bind oxygen reversibly (11)(12)(13). A heme-binding peptide fragment (residues 32-139) of horse heart myoglobin encoded by the central exon and part of the third exon but totally lacking the first exon has been shown to bind both oxygen and carbon monoxide with rate constants similar to those in the native myoglobin (14).…”

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confidence: 99%

Origin of a "bridge" intron in the gene for a two-domain globin.

Naito

Riggs

Vandergon

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Red cells of the clam Barbatia reeveana express two hemoglobins, one composed of 16-to 17-kDa chains and the other of 35-kDa chains. The nucleotide sequence of the cDNA encoding the 35-kDa chain shows that the polypeptide has two very similar heme-binding domains, which are joined without use of an additional bridging sequence. Two novel introns occur in the gene for the two-domain globin: one, the "preceding" intron, is located two bases 5' from the start codon, and the other, a "bridge" intron, separates the DNA sequences encoding the two domains. Close correspondence exists between the 3' end of the preceding intron and the 3' end of the bridge intron and between parts of the 3' noncoding region of the cDNA for the two-domain globin and the 5' end of the bridge intron. These observations indicate that the bridge intron arose by unequal crossing-over between two identical or very similar genes for a single-domain globin. This conclusion, together with the proposal that exons were initially independent "minigenes" [Gilbert, W. (1987) and COOH termini of proteins and provides an explanation for the observation that splice junctions usually map to protein surfaces. They do so because most NH2-and COOH-terminal residues are usually located on or near the surfaces of proteins.

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The relationship between coding sequences and function in haemoglobin

Cited by 106 publications

References 26 publications

Structural and Functional Roles of Modules in Hemoglobin

Structural and Functional Roles of Modules in Hemoglobin

Protein dynamics in minimyoglobin: is the central core of myoglobin the conformational domain?

Origin of a "bridge" intron in the gene for a two-domain globin.

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