A coiled-coil motif that sequesters ions to the hydrophobic core.
Most core residues of coiled coils are hydrophobic. Occasional polar residues are thought to lower stability, but impart structural specificity. The coiled coils of trimeric autotransporter adhesins (TAAs) are conspicuous for their large number of polar residues in position d of the core, which often leads to their prediction as natively unstructured regions. The most frequent residue, asparagine (N@d), can occur in runs of up to 19 consecutive heptads, frequently in the motif [I/V]xxNTxx. In the Salmonella TAA, SadA, the core asparagines form rings of interacting residues with the following threonines, grouped around a central anion. This conformation is observed generally in N@d layers from trimeric coiled coils of known structure. Attempts to impose a different register on the motif show that the asparagines orient themselves specifically into the core, even against conflicting information from flanking domains. When engineered into the GCN4 leucine zipper, N@d layers progressively destabilized the structure, but zippers with 3 N@d layers still folded at high concentration. We propose that N@d layers maintain the coiled coils of TAAs in a soluble, export-competent state during autotransport through the outer membrane. More generally, we think that polar motifs that are both periodic and conserved may often reflect special folding requirements, rather than an unstructured state of the mature proteins.
Hartmann
Marcus D
MD
Department of Protein Evolution, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
Ridderbusch
Oswin
O
Zeth
Kornelius
K
Albrecht
Reinhard
R
Testa
Oli
O
Woolfson
Derek N
DN
Sauer
Guido
G
Dunin-Horkawicz
Stanislaw
S
Lupas
Andrei N
AN
Alvarez
Birte Hernandez
BH
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000737:chemistry* / Q000378:metabolism; D016350:Leucine Zippers; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D019779:Salmonella enterica / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013912:Threonine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D018829:Adhesins, Bacterial; D007477:Ions; D013912:Threonine; D001216:Asparagine