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Updated: May 22, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Homotypic interaction and amino acid distribution of unilaterally conserved transmembrane helices
Christian Lothar Ried1, Sebastian Kube, Jan Kirrbach
1Lehrstuhl für Chemie der Biopolymere, Technische Universität München, Weihenstephaner Berg 3,85354 Freising, Germany.
Abstract:
Formation of non-covalent functional complexes of integral membrane proteins is frequently supported by sequence-specific interaction of their transmembrane helices. Here, we aligned human single-span membrane proteins with orthologs from other eukaryotes. We find that almost half of the human single-span membrane proteins contain a transmembrane helix that exhibits significant non-random unilateral conservation. Furthermore, unilateral conservation of transmembrane domains (TMDs) correlates well with their ability to self-interact. Glycine, polar non-ionizable, and aromatic amino acids are overrepresented in conserved versus non-conserved helix faces. Hence, our genome-wide analysis indicates that these amino acid types generally support interaction of single-span membrane protein TMDs.
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