A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization

Teresa M. Buck, Justin Wagner, Steven Grund, William Skach

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)762-769
Number of pages8
JournalNature Structural and Molecular Biology
Volume14
Issue number8
DOIs
StatePublished - Aug 2007

Fingerprint

Aquaporins
Endoplasmic Reticulum
Hydrogen
Membrane Proteins
Membranes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization. / Buck, Teresa M.; Wagner, Justin; Grund, Steven; Skach, William.

In: Nature Structural and Molecular Biology, Vol. 14, No. 8, 08.2007, p. 762-769.

Research output: Contribution to journalArticle

Buck, Teresa M. ; Wagner, Justin ; Grund, Steven ; Skach, William. / A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization. In: Nature Structural and Molecular Biology. 2007 ; Vol. 14, No. 8. pp. 762-769.
@article{1c4faeb2085541e381a179587873a92a,
title = "A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization",
abstract = "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.",
author = "Buck, {Teresa M.} and Justin Wagner and Steven Grund and William Skach",
year = "2007",
month = "8",
doi = "10.1038/nsmb1275",
language = "English (US)",
volume = "14",
pages = "762--769",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization

AU - Buck, Teresa M.

AU - Wagner, Justin

AU - Grund, Steven

AU - Skach, William

PY - 2007/8

Y1 - 2007/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34547650465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547650465&partnerID=8YFLogxK

U2 - 10.1038/nsmb1275

DO - 10.1038/nsmb1275

M3 - Article

C2 - 17632520

AN - SCOPUS:34547650465

VL - 14

SP - 762

EP - 769

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 8

ER -