The Journal of Membrane Biology

, Volume 245, Issue 11, pp 717–730 | Cite as

Ser/Thr Motifs in Transmembrane Proteins: Conservation Patterns and Effects on Local Protein Structure and Dynamics

Article

Abstract

We combined systematic bioinformatics analyses and molecular dynamics simulations to assess the conservation patterns of Ser and Thr motifs in membrane proteins, and the effect of such motifs on the structure and dynamics of α-helical transmembrane (TM) segments. We find that Ser/Thr motifs are often present in β-barrel TM proteins. At least one Ser/Thr motif is present in almost half of the sequences of α-helical proteins analyzed here. The extensive bioinformatics analyses and inspection of protein structures led to the identification of molecular transporters with noticeable numbers of Ser/Thr motifs within the TM region. Given the energetic penalty for burying multiple Ser/Thr groups in the membrane hydrophobic core, the observation of transporters with multiple membrane-embedded Ser/Thr is intriguing and raises the question of how the presence of multiple Ser/Thr affects protein local structure and dynamics. Molecular dynamics simulations of four different Ser-containing model TM peptides indicate that backbone hydrogen bonding of membrane-buried Ser/Thr hydroxyl groups can significantly change the local structure and dynamics of the helix. Ser groups located close to the membrane interface can hydrogen bond to solvent water instead of protein backbone, leading to an enhanced local solvation of the peptide.

Keywords

Bioinformatics Molecular dynamics Molecular transporters and receptors Ser/Thr motifs Transmembrane proteins 

Notes

Acknowledgements

This research was supported in part by Grant GM-74637 from the National Institute of General Medical Sciences (to S.H.W), the Spanish Ministerio de Ciencia e Innovación (project TIN-2009-13950), the Consejería de Innovación, Investigación y Ciencia de la Junta de Andalucía (project TIC-02788) (to C.M.D.V.), the Marie Curie International Reintegration Award IRG276920/Biol-Transp-Comput (to A.-N.B), and an allocation of computer time from the National Science Foundation through the TeraGrid resources.

Supplementary material

232_2012_9452_MOESM1_ESM.pdf (31.5 mb)
Supplementary material 1 (PDF 13217 kb)

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Computer Science and Artificial IntelligenceUniversity of GranadaGranadaSpain
  2. 2.CITIC-UGRCentro de Investigación en Tecnologías de la Información y de las Comunicaciones de la Universidad de GranadaGranadaSpain
  3. 3.Department of Physiology and BiophysicsUniversity of California, IrvineIrvineUSA
  4. 4.Theoretical Molecular Biophysics, Department of PhysicsFreie Universität BerlinBerlin-DahlemGermany

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