Functional diversity of PH domains: an exhaustive modelling study

Folding & Design
N Blomberg, M Nilges

Abstract

Pleckstrin homology (PH) domains are found in many proteins involved in signal transduction or cytoskeletal organization. The general function for the domain is still unclear; phospholipid binding of some PH domains and a strong electrostatic polarization in the experimental structures suggest a role in localization on membranes. We have analyzed the electrostatic properties and the spatial amino acid distribution from homology models of the entire PH domain family. Despite the sequence divergence, the quality of the models is sufficient for our study. Most PH domains have an electrostatic polarization similar to the experimental structures. but roughly half of the PH domains linked to a Dbl homology domain have very different electrostatic properties. We also found a striking electrostatic complementarity in some internal PH domain repeats. The analysis of the spatial distribution of amino acids identified residues in the phospholipid-binding site of the spectrin and dynamin PH domains as specific for these domains. The mostly conserved electrostatic polarization supports a general function in binding to phospholipid membranes. But the presence of PH domains with opposite polarity suggests that ligands and functions have diver...Continue Reading

References

Apr 1, 1992·Proteins·A L MorrisJ M Thornton
Sep 1, 1995·Nature Structural Biology·K M FergusonJ Schlessinger
Jun 1, 1995·Current Opinion in Structural Biology·M Saraste, M Hyvönen
Nov 1, 1994·Nature Structural Biology·D TimmT Blundell
Feb 1, 1995·Nature Structural Biology·G CasariA Valencia
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·D FushmanD Cowburn
Oct 1, 1994·Current Biology : CB·A K DowningM D Waterfield
Sep 1, 1994·Trends in Biochemical Sciences·T J GibsonE Birney
Jun 23, 1994·Nature·H S YoonS W Fesik
Jun 23, 1994·Nature·M J MaciasH Oschkinat
Sep 1, 1993·Trends in Biochemical Sciences·A MusacchioM Saraste
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
May 27, 1993·Nature·R J HaslamB A Hemmings
Jan 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Shaw
Nov 1, 1995·Proteins·A SaliM Karplus
Jun 20, 1997·Journal of Molecular Biology·S KoshibaS Yokoyama

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Citations

Sep 7, 2002·Journal of Molecular Biology·Jinfeng LiuBurkhard Rost
Jul 16, 2008·The Journal of Chemical Physics·Maciej Długosz, Joanna Trylska
Sep 11, 2014·Interdisciplinary Sciences, Computational Life Sciences·Abhilash MohanGautam Pennathur
Nov 5, 1999·Biochemical and Biophysical Research Communications·M P Okoh, M Vihinen
Nov 30, 2010·Biochimica Et Biophysica Acta·Alberto Fernández-Medarde, Eugenio Santos
Apr 29, 1998·Structure·B Rost
May 5, 2005·Annual Review of Biophysics and Biomolecular Structure·Wonhwa Cho, Robert V Stahelin
Dec 5, 1998·Journal of Molecular Biology·M de RinaldisM Helmer-Citterich
Aug 22, 2003·Protein Science : a Publication of the Protein Society·Shaneen M Singh, Diana Murray
Apr 29, 1999·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·L CorderoL W Ayers
Feb 11, 2009·Evolutionary Bioinformatics Online·Najl V ValeyevCharlotte Deane
Dec 5, 1998·Biochimica Et Biophysica Acta·M J BottomleyG Panayotou
May 29, 2000·Biochimica Et Biophysica Acta·M SubramanianP K Kinnunen

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