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Folding of Aplysia limacina apomyoglobin involves an intermediate in common with other evolutionarily distant globins.
Biochemistry. 2004 Jan 13; 43(1):230-6.B

Abstract

In the globin family, similarities in the folding mechanism have been found among different mammalian apomyoglobins (apoMb). The best-characterized intermediate of sperm whale apoMb, called I(AGH), is mainly stabilized by nativelike contacts among the A, G, and H helices involving a cluster of hydrophobic residues that includes two conserved tryptophans. To verify the hypothesis of a common intermediate in the folding of all members of the globin family, we have extensively studied a site-directed mutant of the myoglobin from Aplysia limacina, distantly related to the mammalian counterpart, in which one of the two tryptophans in the A-G-H cluster [i.e., Trp(H8)130] has been mutated to tyrosine. The results presented here show that this mutation destabilizes both the native state and the acid intermediate I(A) but exerts little or no effect on the thermally stable core of an intermediate species (called I(T)) peculiar to Aplysia apomyoglobin. Dynamic quenching of Trp emission by acrylamide provides information on the accessibility of the chromophores at the native and the intermediate states of wild-type and mutant Aplysia apomyoglobin, consistent with the thermodynamics. Our results agree well with those obtained for the corresponding topological position of apomyoglobin from sperm whale and clearly show that the H8 position is involved in the stabilization of the main intermediate in both apoproteins. This residue thus plays a role which is evolutionarily conserved in the globin family from invertebrates to mammals; our results support the contention that the A-G-H cluster is important in the folding pathway of different globins.

Authors+Show Affiliations

Istituto Pasteur-Fondazione Cenci Bolognetti, Università di Roma La Sapienza, Piazzale A. Moro 5, 00185 Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14705950

Citation

Musto, Raffaella, et al. "Folding of Aplysia Limacina Apomyoglobin Involves an Intermediate in Common With Other Evolutionarily Distant Globins." Biochemistry, vol. 43, no. 1, 2004, pp. 230-6.
Musto R, Bigotti MG, Travaglini-Allocatelli C, et al. Folding of Aplysia limacina apomyoglobin involves an intermediate in common with other evolutionarily distant globins. Biochemistry. 2004;43(1):230-6.
Musto, R., Bigotti, M. G., Travaglini-Allocatelli, C., Brunori, M., & Cutruzzolà, F. (2004). Folding of Aplysia limacina apomyoglobin involves an intermediate in common with other evolutionarily distant globins. Biochemistry, 43(1), 230-6.
Musto R, et al. Folding of Aplysia Limacina Apomyoglobin Involves an Intermediate in Common With Other Evolutionarily Distant Globins. Biochemistry. 2004 Jan 13;43(1):230-6. PubMed PMID: 14705950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folding of Aplysia limacina apomyoglobin involves an intermediate in common with other evolutionarily distant globins. AU - Musto,Raffaella, AU - Bigotti,Maria Giulia, AU - Travaglini-Allocatelli,Carlo, AU - Brunori,Maurizio, AU - Cutruzzolà,Francesca, PY - 2004/1/7/pubmed PY - 2004/5/13/medline PY - 2004/1/7/entrez SP - 230 EP - 6 JF - Biochemistry JO - Biochemistry VL - 43 IS - 1 N2 - In the globin family, similarities in the folding mechanism have been found among different mammalian apomyoglobins (apoMb). The best-characterized intermediate of sperm whale apoMb, called I(AGH), is mainly stabilized by nativelike contacts among the A, G, and H helices involving a cluster of hydrophobic residues that includes two conserved tryptophans. To verify the hypothesis of a common intermediate in the folding of all members of the globin family, we have extensively studied a site-directed mutant of the myoglobin from Aplysia limacina, distantly related to the mammalian counterpart, in which one of the two tryptophans in the A-G-H cluster [i.e., Trp(H8)130] has been mutated to tyrosine. The results presented here show that this mutation destabilizes both the native state and the acid intermediate I(A) but exerts little or no effect on the thermally stable core of an intermediate species (called I(T)) peculiar to Aplysia apomyoglobin. Dynamic quenching of Trp emission by acrylamide provides information on the accessibility of the chromophores at the native and the intermediate states of wild-type and mutant Aplysia apomyoglobin, consistent with the thermodynamics. Our results agree well with those obtained for the corresponding topological position of apomyoglobin from sperm whale and clearly show that the H8 position is involved in the stabilization of the main intermediate in both apoproteins. This residue thus plays a role which is evolutionarily conserved in the globin family from invertebrates to mammals; our results support the contention that the A-G-H cluster is important in the folding pathway of different globins. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/14705950/Folding_of_Aplysia_limacina_apomyoglobin_involves_an_intermediate_in_common_with_other_evolutionarily_distant_globins_ L2 - https://doi.org/10.1021/bi035319l DB - PRIME DP - Unbound Medicine ER -