A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization.
Aquaporin (AQP) folding in the endoplasmic reticulum is characterized by two distinct pathways of membrane insertion that arise from divergent residues within the second transmembrane segment. We now show that in AQP1 these residues (Asn49 and Lys51) interact with Asp185 at the C terminus of TM5 to form a polar, quaternary structural motif that influences multiple stages of folding. Asn49 and Asp185 form an intramolecular hydrogen bond needed for proper helical packing, monomer formation and function. In contrast, Lys51 interacts with Asp185 on an adjacent monomer to stabilize the AQP1 tetramer. Although these residues are unique to AQP1, they share a highly conserved architecture whose functional properties can be transferred to other family members. These findings suggest a general mechanism by which evolutionary divergence of membrane proteins can confer new functional properties via alternative folding pathways that give rise to a common final structure.
Buck
Teresa M
TM
Department of Biochemistry and Molecular Biology, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97239, USA.
Wagner
Justin
J
Grund
Steven
S
Skach
William R
WR
D020816:Amino Acid Motifs; D051398:Aquaporin 1 / Q000737:chemistry*; D001216:Asparagine / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding
C496020:AQP1 protein, human; D051398:Aquaporin 1; D001216:Asparagine; D008239:Lysine