Title: Extent of Structural Asymmetry in Homodimeric Proteins: Prevalence and Relevance
Authors: LS, Swapna *
Kuchi, Srikeerthana *
N, Srinivasan # ×
Issue Date: 22-May-2012
Publisher: Public Library of Sciene
Series Title: PLoS One vol:7 issue:5
Article number: e36688
Abstract: Most homodimeric proteins have symmetric structure. Although symmetry is known to confer structural and functional
advantage, asymmetric organization is also observed. Using a non-redundant dataset of 223 high-resolution crystal
structures of biologically relevant homodimers, we address questions on the prevalence and significance of asymmetry. We
used two measures to quantify global and interface asymmetry, and assess the correlation of several molecular and
structural parameters with asymmetry. We have identified rare cases (11/223) of biologically relevant homodimers with
pronounced global asymmetry. Asymmetry serves as a means to bring about 2:1 binding between the homodimer and
another molecule; it also enables cellular signalling arising from asymmetric macromolecular ligands such as DNA. Analysis
of these cases reveals two possible mechanisms by which possible infinite array formation is prevented. In case of
homodimers associating via non-topologically equivalent surfaces in their tertiary structures, ligand-dependent mechanisms
are used. For stable dimers binding via large surfaces, ligand-dependent structural change regulates polymerisation/
depolymerisation; for unstable dimers binding via smaller surfaces that are not evolutionarily well conserved, dimerisation
occurs only in the presence of the ligand. In case of homodimers associating via interaction surfaces with parts of the
surfaces topologically equivalent in the tertiary structures, steric hindrance serves as the preventive mechanism of infinite
array. We also find that homodimers exhibiting grossly symmetric organization rarely exhibit either perfect local symmetry
or high local asymmetry. Binding of small ligands at the interface does not cause any significant variation in interface
asymmetry. However, identification of biologically relevant interface asymmetry in grossly symmetric homodimers is
confounded by the presence of similar small magnitude changes caused due to artefacts of crystallisation. Our study provides new insights regarding accommodation of asymmetry in homodimers.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
* (joint) first author
× corresponding author
# (joint) last author

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