The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity

Milica Popovica; A. Schouten; Marije Rensen-de Leeuw; Holger Rehmann

doi:10.1016/j.jsb.2015.12.006

The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity

Milica Popovica, A. Schouten, Marije Rensen-de Leeuw, Holger Rehmann^*

^*Corresponding author for this work

University Medical Center Utrecht

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

CDC25 homology domain (CDC25-HD) containing Guanine Nucleotide Exchange Factors (GEFs) initiate signalling by small G-proteins of the Ras-family. Each GEF acts on a small subset of the G-proteins only, thus providing signalling selectivity. Rlf is a GEF with selectivity for the G-proteins RalA and RalB. Here the crystal structure of Rlf in complex with Ral is determined. The Rlf·Ral complex crystallised into two different crystal forms, which represent different steps of the exchange reaction. Thereby general insight in the CDC25-HD catalysed nucleotide exchange is obtained. In addition, the basis for the selectivity of the interaction is investigated. The exchange activity is monitored by the use of recombinant proteins. Selectivity determinants in the binding interface are identified and confirmed by a mutational study.

Original language	English
Pages (from-to)	106–114
Number of pages	9
Journal	Journal of Molecular Structure
Volume	193
Issue number	2
DOIs	https://doi.org/10.1016/j.jsb.2015.12.006
Publication status	Published - Feb 2016

Keywords

Ras-family of G-proteins
Induced fit
CDC25-homology domain
Guanine nucleotide exchange reaction

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10.1016/j.jsb.2015.12.006

0112X-mainFinal published version, 2.17 MBLicence: Taverne

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title = "The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity",

abstract = "CDC25 homology domain (CDC25-HD) containing Guanine Nucleotide Exchange Factors (GEFs) initiate signalling by small G-proteins of the Ras-family. Each GEF acts on a small subset of the G-proteins only, thus providing signalling selectivity. Rlf is a GEF with selectivity for the G-proteins RalA and RalB. Here the crystal structure of Rlf in complex with Ral is determined. The Rlf·Ral complex crystallised into two different crystal forms, which represent different steps of the exchange reaction. Thereby general insight in the CDC25-HD catalysed nucleotide exchange is obtained. In addition, the basis for the selectivity of the interaction is investigated. The exchange activity is monitored by the use of recombinant proteins. Selectivity determinants in the binding interface are identified and confirmed by a mutational study.",

keywords = "Ras-family of G-proteins, Induced fit, CDC25-homology domain, Guanine nucleotide exchange reaction",

author = "Milica Popovica and A. Schouten and {Rensen-de Leeuw}, Marije and Holger Rehmann",

year = "2016",

month = feb,

doi = "10.1016/j.jsb.2015.12.006",

language = "English",

volume = "193",

pages = "106–114",

journal = "Journal of Molecular Structure",

issn = "0022-2860",

publisher = "Elsevier BV",

number = "2",

}

Popovica, M, Schouten, A, Rensen-de Leeuw, M & Rehmann, H 2016, 'The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity', Journal of Molecular Structure, vol. 193, no. 2, pp. 106–114. https://doi.org/10.1016/j.jsb.2015.12.006

The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity. / Popovica, Milica; Schouten, A.; Rensen-de Leeuw, Marije et al.
In: Journal of Molecular Structure, Vol. 193, No. 2, 02.2016, p. 106–114.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity

AU - Popovica, Milica

AU - Schouten, A.

AU - Rensen-de Leeuw, Marije

AU - Rehmann, Holger

PY - 2016/2

Y1 - 2016/2

N2 - CDC25 homology domain (CDC25-HD) containing Guanine Nucleotide Exchange Factors (GEFs) initiate signalling by small G-proteins of the Ras-family. Each GEF acts on a small subset of the G-proteins only, thus providing signalling selectivity. Rlf is a GEF with selectivity for the G-proteins RalA and RalB. Here the crystal structure of Rlf in complex with Ral is determined. The Rlf·Ral complex crystallised into two different crystal forms, which represent different steps of the exchange reaction. Thereby general insight in the CDC25-HD catalysed nucleotide exchange is obtained. In addition, the basis for the selectivity of the interaction is investigated. The exchange activity is monitored by the use of recombinant proteins. Selectivity determinants in the binding interface are identified and confirmed by a mutational study.

AB - CDC25 homology domain (CDC25-HD) containing Guanine Nucleotide Exchange Factors (GEFs) initiate signalling by small G-proteins of the Ras-family. Each GEF acts on a small subset of the G-proteins only, thus providing signalling selectivity. Rlf is a GEF with selectivity for the G-proteins RalA and RalB. Here the crystal structure of Rlf in complex with Ral is determined. The Rlf·Ral complex crystallised into two different crystal forms, which represent different steps of the exchange reaction. Thereby general insight in the CDC25-HD catalysed nucleotide exchange is obtained. In addition, the basis for the selectivity of the interaction is investigated. The exchange activity is monitored by the use of recombinant proteins. Selectivity determinants in the binding interface are identified and confirmed by a mutational study.

KW - Ras-family of G-proteins

KW - Induced fit

KW - CDC25-homology domain

KW - Guanine nucleotide exchange reaction

U2 - 10.1016/j.jsb.2015.12.006

DO - 10.1016/j.jsb.2015.12.006

M3 - Article

SN - 0022-2860

VL - 193

SP - 106

EP - 114

JO - Journal of Molecular Structure

JF - Journal of Molecular Structure

IS - 2

ER -

The structure of the Guanine Nucleotide Exchange Factor Rlf in complex with the small G-protein Ral identifies conformational intermediates of the exchange reaction and the basis for the selectivity

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Keywords

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