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Title: Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

Abstract

F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here in this paper, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. In conclusion, our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence.

Authors:
 [1];  [2];  [3];  [4];  [1];  [5];  [1]
  1. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Biochemistry and Biophysics
  2. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Biochemistry and Biophysics; Kolltan Pharmaceuticals, Inc., New Haven, CT (United States)
  3. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Biochemistry and Biophysics; Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Physiology; Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Biology
  4. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Biochemistry and Biophysics; Dyax Corporation, Burlington, MA (United States)
  5. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Biochemistry and Biophysics; Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine, Dept. of Physiology
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Cancer Institute (NCI); National Science Foudnation (NSF); National Institutes of Health (NIH)
OSTI Identifier:
1236716
Alternate Identifier(s):
OSTI ID: 1182313; OSTI ID: 1233884
Grant/Contract Number:  
W-31-109-ENG-38; DMR-0225180; R01-GM056846; RR-01646; 61-1316; T32-GM008275
Resource Type:
Journal Article: Published Article
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 23; Journal Issue: 2; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Moravcevic, Katarina, Alvarado, Diego, Schmitz, Karl R., Kenniston, Jon A., Mendrola, Jeannine M., Ferguson, Kathryn M., and Lemmon, Mark A. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site. United States: N. p., 2015. Web. doi:10.1016/j.str.2014.12.009.
Moravcevic, Katarina, Alvarado, Diego, Schmitz, Karl R., Kenniston, Jon A., Mendrola, Jeannine M., Ferguson, Kathryn M., & Lemmon, Mark A. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site. United States. doi:10.1016/j.str.2014.12.009.
Moravcevic, Katarina, Alvarado, Diego, Schmitz, Karl R., Kenniston, Jon A., Mendrola, Jeannine M., Ferguson, Kathryn M., and Lemmon, Mark A. Thu . "Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site". United States. doi:10.1016/j.str.2014.12.009.
@article{osti_1236716,
title = {Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site},
author = {Moravcevic, Katarina and Alvarado, Diego and Schmitz, Karl R. and Kenniston, Jon A. and Mendrola, Jeannine M. and Ferguson, Kathryn M. and Lemmon, Mark A.},
abstractNote = {F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here in this paper, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. In conclusion, our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence.},
doi = {10.1016/j.str.2014.12.009},
journal = {Structure},
number = 2,
volume = 23,
place = {United States},
year = {Thu Jan 22 00:00:00 EST 2015},
month = {Thu Jan 22 00:00:00 EST 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.str.2014.12.009

Citation Metrics:
Cited by: 13 works
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