Abstract
Motivation: Most integral membrane proteins form dimeric or oligomeric complexes. Oligomerization is frequently supported by the noncovalent interaction of transmembrane helices. It is currently not clear how many high-affinity transmembrane domains (TMD) exist in a proteome and how specific their interactions are with respect to preferred contacting faces and their underlying residue motifs. Results: We first identify a threshold of 55% sequence similarity, which demarcates the border between meaningful alignments of TMDs and chance alignments. Clustering the human single-span membrane proteome using this threshold groups ∼40% of the TMDs. The homotypic interaction of the TMDs representing the 33 largest clusters was systematically investigated under standardized conditions. The results reveal a broad distribution of relative affinities. High relative affinity frequently coincides with (i) the existence of a preferred helix-helix interface and (ii) sequence specificity as indicated by reduced affinity after mutating conserved residues.
| Original language | English |
|---|---|
| Pages (from-to) | 1623-1630 |
| Number of pages | 8 |
| Journal | Bioinformatics |
| Volume | 29 |
| Issue number | 13 |
| DOIs | |
| State | Published - 1 Jul 2013 |
Bibliographical note
Funding Information:Funding: This work was supported by the Deutsche Forschungsgemeinschaft (grant La699/13-1 to D.L. and to I.A.), the Center for Integrative Protein Science Munich, the Deutsche Akademische Austauschdienst, and the TUM Graduate School.