Common occurrence of internal repeat symmetry in membrane proteins

Abstract

Symmetry plays significant roles in protein structure and function. Particularly, symmetric interfaces are known to act as switches for twostate conformational change. Membrane proteins often undergo twostate conformational change during the transport process of ion channels or the active/inactive transitions in receptors. Here, we provide the first comprehensive analyses of internal repeat symmetry in membrane proteins. We examined the known membrane protein structures and found that, remarkably, nearly half of them have internal repeat symmetry. Moreover, we found that the conserved cores of these internal repeats are positioned at the interface of symmetric units when they are mapped on structures. Because of the large sequence divergence that occurs between internal repeats, the inherent symmetry present in protein sequences often has only been detected after structure determination. We therefore developed a sensitive procedure to predict the internal repeat symmetry from sequence information and identified 4653 proteins that are likely to have internal repeat symmetry. Proteins 2008; 71:68-80. V V C 2007 Wiley-Liss, Inc.

Systematic Detection of Internal Symmetry in Proteins Using CE-Symm

“…Symmetry is also disproportionately frequent among membrane superfamilies, in agreement with previous observations [50, 51]. Membrane proteins often contain additional quaternary symmetry in addition to the internal symmetry within individual domains.…”

Coils in the Membrane Core Are Conserved and Functionally Important

“…Compared to other helical TM proteins, channels and transporters have shown an elevated number of reentrant regions 16 and more internal structural symmetry due to duplication events. 18 They are also more loosely packed due to the presence of internal cavities, 19 are enriched with weak hydrogen bonds 20 and prefer a different type of helix-helix structural motif. 20 Here, we extend the studies on nonstandard features in membrane proteins using a previously ignored observation that there exist about 5-10% coil residues in the membrane core 15 (Fig.…”

Bioinformatic approaches for the structure and function of membrane proteins

“…Nevertheless, computational methods can guide experiment planning and dataset interpretation by providing information on TM helix topology, helix-helix interactions, and functionally important regions of membrane proteins. Moreover, the integration of evolutionary information can increase the understanding of the structure and function of membrane proteins (77). We expect that rapid progress in the development of bioinformatic approaches will expand our knowledge of the sequence-structure-function relationship of membrane proteins.…”

“…Therefore, the development of comparative genomic approaches provides an alternative approach for the prediction of membrane protein function. These approaches analyze the conservation patterns of membrane protein family members in order to characterize the function of unannotated protein sequences (77). Information on protein-protein interactions and phylogenetic analysis were also used in the determination of protein function (50,87).…”