Conservation of folding pathways in evolutionarily distant globin sequences.
To test the hypothesis that the folding pathways of evolutionarily related proteins with similar three-dimensional structures but widely different sequences should be similar, the folding pathway of apoleghemoglobin has been characterized using stopped-flow circular dichroism, heteronuclear NMR pulse labeling techniques and mass spectrometry. The pathway of folding was found to differ significantly from that of a protein of the same family, apomyoglobin, although both proteins appear to fold through helical burst phase intermediates. For leghemoglobin, the burst phase intermediate exhibits stable helical structure in the G and H helices, together with a small region in the center of the E helix. The A and B helices are not stabilized until later stages of the folding process. The structure of the burst phase folding intermediate thus differs from that of apomyoglobin, in which stable helical structure is formed in the A, B, G and H helix regions.
Nishimura
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C
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Prytulla
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S
Dyson
H J
HJ
Wright
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D019143:Evolution, Molecular; D005914:Globins / Q000737:chemistry* / Q000378:metabolism*; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007874:Leghemoglobin / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
D001059:Apoproteins; D006420:Hemeproteins; D007874:Leghemoglobin; D009211:Myoglobin; D014508:Urea; D005914:Globins