Structural basis for small G protein effector interaction of Ras-related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1).

The Journal of Biological Chemistry
Xiaofeng LiTitus J Boggon

Abstract

Cerebral cavernous malformations (CCMs) affect 0.1-0.5% of the population resulting in leaky vasculature and severe neurological defects. KRIT1 (Krev interaction trapped-1) mutations associate with ∼40% of familial CCMs. KRIT1 is an effector of Ras-related protein 1 (Rap1) GTPase. Rap1 relocalizes KRIT1 from microtubules to cell membranes to impact integrin activation, potentially important for CCM pathology. We report the 1.95 Å co-crystal structure of KRIT1 FERM domain in complex with Rap1. Rap1-KRIT1 interaction encompasses an extended surface, including Rap1 Switch I and II and KRIT1 FERM F1 and F2 lobes. Rap1 binds KRIT1-F1 lobe using a GTPase-ubiquitin-like fold interaction but binds KRIT1-F2 lobe by a novel interaction. Point mutagenesis confirms the interaction. High similarity between KRIT1-F2/F3 and talin is revealed. Additionally, the mechanism for FERM domains acting as GTPase effectors is suggested. Finally, structure-based alignment of each lobe suggests classification of FERM domains as ERM-like and TMFK-like (talin-myosin-FAK-KRIT-like) and that FERM lobes resemble domain "modules."

References

Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·M GünelR P Lifton
Jul 1, 1994·Biopolymers·R NorelR Nussinov
Dec 20, 1993·Journal of Molecular Biology·M C Lawrence, P M Colman
Nov 1, 1995·Trends in Biochemical Sciences·L Holm, C Sander
Aug 1, 1996·Nature Structural Biology·N NassarA Wittinghofer
Jun 17, 1998·Nature Structural Biology·L HuangS H Kim
Mar 31, 1999·Trends in Biochemical Sciences·J A GiraultI Callebaut
Jul 15, 2000·Animal Genetics·L R RitzC Gaillard
Jan 11, 2000·Nucleic Acids Research·R A Laskowski
Sep 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·A PerrakisV S Lamzin
Jul 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Murat GunelRichard P Lifton
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Jan 22, 2003·Molecular Cell·Begoña García-AlvarezRobert C Liddington
Jun 25, 2004·Nucleic Acids Research·Ian W DavisDavid C Richardson
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 11, 2005·Molecular Biology of the Cell·Henri-Noël FournierCorinne Albiges-Rizo
Mar 23, 2005·Current Opinion in Cell Biology·Johannes L Bos
Apr 5, 2005·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoyRandy J Read
Mar 31, 2006·Journal of Medical Genetics·N Revencu, M Vikkula
Apr 18, 2006·Structure·Shin-ichi TerawakiToshio Hakoshima
Sep 19, 2006·Current Biology : CB·Jaewon HanMark H Ginsberg
Dec 1, 2006·Journal of Molecular Biology·Qianzhi LiJohn J G Tesmer
Jun 2, 2007·Cell·Johannes L BosAlfred Wittinghofer
Jun 19, 2007·Cell·Daniel LiethaMichael J Eck
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Aug 19, 2007·Methods in Enzymology·Yatish LadDavid A Calderwood
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Oct 24, 2007·The Journal of Cell Biology·Angela GladingMark H Ginsberg
Mar 1, 2008·The EMBO Journal·Andrea ScrimaAlfred Wittinghofer
Sep 25, 2008·Neurosurgery·Jun ZhangRichard E Clatterbuck
Nov 11, 2008·Experimental Cell Research·Floriana FrancalanciSaverio Francesco Retta
Dec 19, 2008·The Journal of Biological Chemistry·Judith H Raaijmakers, Johannes L Bos
Dec 23, 2008·The Journal of Biological Chemistry·Ho-Sup LeeMark H Ginsberg
Jan 23, 2009·Biochimica Et Biophysica Acta·Willem-Jan PannekoekJohannes L Bos

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Citations

Aug 6, 2013·Experimental Cell Research·Magdalena Chrzanowska-Wodnicka
Feb 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rajesh GhaiBrett M Collins
May 23, 2013·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Weizhi Liu, Titus J Boggon
Nov 30, 2013·Cellular and Molecular Life Sciences : CMLS·Oriana S Fisher, Titus J Boggon
Apr 2, 2015·Critical Reviews in Biochemistry and Molecular Biology·Helen R Mott, Darerca Owen
Aug 21, 2015·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Shin-Ichi TerawakiToshio Hakoshima
Jan 28, 2016·Protein Science : a Publication of the Protein Society·Hui Sun Lee, Wonpil Im
Apr 10, 2014·Cell Adhesion & Migration·Maaike C W van den Berg, Boudewijn M T Burgering
Aug 30, 2013·Communicative & Integrative Biology·Manishha Patel, Jean-François Côté
Jan 16, 2013·Molecular Cell·Weizhi LiuTitus J Boggon
May 12, 2016·Proceedings of the National Academy of Sciences of the United States of America·Vicente José Planelles-HerreroMargaret A Titus
Oct 30, 2016·American Journal of Medical Genetics. Part a·Ivo J H M de VosMaurice A M van Steensel
Dec 30, 2015·PloS One·Magdalena Chrzanowska-WodnickaKevin J Whitehead
Sep 8, 2020·The FEBS Journal·Amy L Stiegler, Titus J Boggon
Sep 12, 2015·Oncotarget·Xiaofeng LiTitus J Boggon
Nov 26, 2020·Open Biology·Valerie L Su, David A Calderwood
Jan 15, 2021·Journal of Cell Science·Elisa De LucaSaverio Francesco Retta
Feb 1, 2014·Journal of Cell Science·Kyle M DraheimDavid A Calderwood
May 13, 2021·FASEB BioAdvances·Miguel Alejandro Lopez-RamirezAlexandre R Gingras

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