Plasticity within the obligatory folding nucleus of an immunoglobulin-like domain.
A number of beta-sandwich immunoglobulin-like domains have been shown to fold using a set of structurally equivalent residues that form a folding nucleus deep within the core of the protein. Formation of this nucleus is sufficient to establish the complex Greek key topology of the native state. These nucleating residues are highly conserved within the immunoglobulin superfamily, but are less well conserved in the fibronectin type III (fnIII) superfamily, where the requirement is simply to have four interacting hydrophobic residues. However, there are rare examples where this nucleation pattern is absent. In this study, we have investigated the folding of a novel member of the fnIII superfamily whose nucleus appears to lack one of the four buried hydrophobic residues. We show that the folding mechanism is unaltered, but the folding nucleus has moved within the hydrophobic core.
Lappalainen
Ilkka
I
University of Cambridge Department of Chemistry, MRC Centre for Protein Engineering, Lensfield Rd, Cambridge CB2 1EW, UK.
Hurley
Michael G
MG
Clarke
Jane
J
D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry; D001407:Bacillus / Q000201:enzymology / Q000235:genetics; D002688:Chitinases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017124:Conserved Sequence; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011489:Protein Denaturation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019063:Tenascin / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013816:Thermodynamics
D024322:Amino Acids, Aromatic; D005353:Fibronectins; D007136:Immunoglobulins; D019063:Tenascin; D002688:Chitinases