Structures of the L27 Domain of Disc Large Homologue 1 Protein Illustrate a Self-Assembly Module

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Disc large 1 (Dlg1) proteins, members of the MAGUK protein family, are linked to cell polarity via their participation in multiprotein assemblies. At their N-termini, Dlg1 proteins contain a L27 domain. Typically, the L27 domains participate in the formation of obligate hetero-oligomers with the L27 domains from their cognate partners. Among the MAGUKs, Dlg1 proteins exist as homo-oligomers, and the oligomerization is solely dependent on the L27 domain. Here we provide biochemical and structural evidence of homodimerization via the L27 domain of Dlg1 from Drosophila melanogaster. The structure reveals that the core of the dimer is formed by a distinctive six-helix assembly, involving all three conserved helices from each subunit (monomer). The homodimer interface is extended by the C-terminal tail of the L27 domain of Dlg1, which forms a two-stranded antiparallel β-sheet. The structure reconciles and provides a structural context for a large body of available mutational data. From our analyses, we conclude that the observed L27 homodimerization is most likely a feature unique to the Dlg1 orthologs within the MAGUK family.

Original languageEnglish (US)
Pages (from-to)1293-1305
Number of pages13
JournalBiochemistry
Volume57
Issue number8
DOIs
StatePublished - Feb 27 2018

Fingerprint

Self assembly
Oligomers
Guanylate Kinases
Cell Polarity
Oligomerization
Proteins
Drosophila melanogaster
Dimers
Tail
Monomers

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structures of the L27 Domain of Disc Large Homologue 1 Protein Illustrate a Self-Assembly Module. / Ghosh, Agnidipta; Ramagopal, Udupi A.; Bonanno, Jeffrey B.; Brenowitz, Michael D.; Almo, Steven C.

In: Biochemistry, Vol. 57, No. 8, 27.02.2018, p. 1293-1305.

Research output: Contribution to journalArticle

@article{b9cfcd6b78074b1eaa62476c152e8e08,
title = "Structures of the L27 Domain of Disc Large Homologue 1 Protein Illustrate a Self-Assembly Module",
abstract = "Disc large 1 (Dlg1) proteins, members of the MAGUK protein family, are linked to cell polarity via their participation in multiprotein assemblies. At their N-termini, Dlg1 proteins contain a L27 domain. Typically, the L27 domains participate in the formation of obligate hetero-oligomers with the L27 domains from their cognate partners. Among the MAGUKs, Dlg1 proteins exist as homo-oligomers, and the oligomerization is solely dependent on the L27 domain. Here we provide biochemical and structural evidence of homodimerization via the L27 domain of Dlg1 from Drosophila melanogaster. The structure reveals that the core of the dimer is formed by a distinctive six-helix assembly, involving all three conserved helices from each subunit (monomer). The homodimer interface is extended by the C-terminal tail of the L27 domain of Dlg1, which forms a two-stranded antiparallel β-sheet. The structure reconciles and provides a structural context for a large body of available mutational data. From our analyses, we conclude that the observed L27 homodimerization is most likely a feature unique to the Dlg1 orthologs within the MAGUK family.",
author = "Agnidipta Ghosh and Ramagopal, {Udupi A.} and Bonanno, {Jeffrey B.} and Brenowitz, {Michael D.} and Almo, {Steven C.}",
year = "2018",
month = "2",
day = "27",
doi = "10.1021/acs.biochem.7b01074",
language = "English (US)",
volume = "57",
pages = "1293--1305",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Structures of the L27 Domain of Disc Large Homologue 1 Protein Illustrate a Self-Assembly Module

AU - Ghosh, Agnidipta

AU - Ramagopal, Udupi A.

AU - Bonanno, Jeffrey B.

AU - Brenowitz, Michael D.

AU - Almo, Steven C.

PY - 2018/2/27

Y1 - 2018/2/27

N2 - Disc large 1 (Dlg1) proteins, members of the MAGUK protein family, are linked to cell polarity via their participation in multiprotein assemblies. At their N-termini, Dlg1 proteins contain a L27 domain. Typically, the L27 domains participate in the formation of obligate hetero-oligomers with the L27 domains from their cognate partners. Among the MAGUKs, Dlg1 proteins exist as homo-oligomers, and the oligomerization is solely dependent on the L27 domain. Here we provide biochemical and structural evidence of homodimerization via the L27 domain of Dlg1 from Drosophila melanogaster. The structure reveals that the core of the dimer is formed by a distinctive six-helix assembly, involving all three conserved helices from each subunit (monomer). The homodimer interface is extended by the C-terminal tail of the L27 domain of Dlg1, which forms a two-stranded antiparallel β-sheet. The structure reconciles and provides a structural context for a large body of available mutational data. From our analyses, we conclude that the observed L27 homodimerization is most likely a feature unique to the Dlg1 orthologs within the MAGUK family.

AB - Disc large 1 (Dlg1) proteins, members of the MAGUK protein family, are linked to cell polarity via their participation in multiprotein assemblies. At their N-termini, Dlg1 proteins contain a L27 domain. Typically, the L27 domains participate in the formation of obligate hetero-oligomers with the L27 domains from their cognate partners. Among the MAGUKs, Dlg1 proteins exist as homo-oligomers, and the oligomerization is solely dependent on the L27 domain. Here we provide biochemical and structural evidence of homodimerization via the L27 domain of Dlg1 from Drosophila melanogaster. The structure reveals that the core of the dimer is formed by a distinctive six-helix assembly, involving all three conserved helices from each subunit (monomer). The homodimer interface is extended by the C-terminal tail of the L27 domain of Dlg1, which forms a two-stranded antiparallel β-sheet. The structure reconciles and provides a structural context for a large body of available mutational data. From our analyses, we conclude that the observed L27 homodimerization is most likely a feature unique to the Dlg1 orthologs within the MAGUK family.

UR - http://www.scopus.com/inward/record.url?scp=85042708012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042708012&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.7b01074

DO - 10.1021/acs.biochem.7b01074

M3 - Article

VL - 57

SP - 1293

EP - 1305

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 8

ER -