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SUMMARY:EPFL BioE Talks SERIES  "Activation and Inhibition of an Unusual G
  Protein-Coupled Receptor"
DTSTART:20231127T160000
DTEND:20231127T170000
DTSTAMP:20260916T131013Z
UID:6cd0496819d252dadf897b2c9600cb83eb17892cfc341a0f7de2b10c
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Andrew Kruse\, Harvard Medical School\, Boston\, MA (USA
 )\nWEEKLY EPFL BIOE TALKS SERIES\n\nAbstract:\nThe relaxin family peptide 
 receptor 1 (RXFP1) is the receptor for relaxin-2\, an important regulator 
 of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G p
 rotein-coupled receptor (GPCR) with an ectodomain consisting of a low-dens
 ity lipoprotein receptor class A (LDLa) module and leucine-rich repeats. T
 he mechanism of RXFP1 signal transduction is clearly distinct from that of
  other GPCRs\, but remains very poorly understood. We determined the cryo-
 electron microscopy structure of active-state human RXFP1 bound to a singl
 e-chain analog of the endogenous agonist relaxin-2 and the heterotrimeric 
 Gs protein. Evolutionary coupling analysis and structure-guided functional
  experiments reveal that RXFP1 signals through a mechanism of autoinhibiti
 on by the ectodomain. More recently\, we have determined the structure of 
 RXFP1 in an inactive state and an active-state structure of RXFP1 bound to
  a small-molecule agonist. Our results explain how this unusual GPCR funct
 ions\, and have enabled rational engineering of a long-acting agonist that
  is in clinical development.\n\nBio:\nDr. Kruse is a Professor of Biologic
 al Chemistry and Molecular Pharmacology at Harvard Medical School. His res
 earch focuses on the structure and function of transmembrane receptors\, u
 sing a combination of biophysical and cell biological approaches. Research
  in the Kruse lab also makes extensive use of combinatorial protein engine
 ering methods such as yeast surface display of single-domain antibody frag
 ments.\n\nDr. Kruse began his independent career as an Assistant Professor
  at Harvard Medical School in 2014. Key research accomplishments include d
 efining the structural basis for agonist action at the angiotensin II type
  1 receptor and other G protein-protein coupled receptors (GPCRs)\, clonin
 g the sigma-2 receptor\, and determining the first structure of a tetraspa
 nin protein and showing how it regulates B cell activation. The Kruse lab 
 also developed a single-domain antibody fragment discovery platform. Dr. K
 ruse is a co-founder of Tectonic Therapeutic\, a biotechnology company\, a
 nd the Institute for Protein Innovation\, a non-profit research organizati
 on. He has received awards including an Amgen Young Investigator Award (20
 19)\, an Alfred P. Sloan Research Fellowship (2017)\, a Vallee Scholars Aw
 ard (2016)\, and an NIH Director’s Early Independence Award (2015). He r
 eceived B.S. degrees in Mathematics and Biochemistry from the University o
 f Minnesota in 2009\, and completed a Ph.D. in Structural Biology at Stanf
 ord University in 2014\, where he trained with Dr. Brian Kobilka.\n\n\nZoo
 m link (with one-time registration for the whole series) for attending rem
 otely: https://go.epfl.ch/EPFLBioETalks\n\n\nInstructions for 1st-year Ph.
 D. students who are under EDBB’s mandatory seminar attendance rule:\nIF 
 you are not attending in-person in the room\, please make sure to\n\n	send
  D. Reinhard a note before noon on seminar day\, informing that you plan t
 o attend the talk online\, and\n	be signed in on Zoom with a recognizable 
 user name (not a pseudonym making it difficult or impossible to be identif
 ied).\n\nStudents attending the seminar in-person should collect a confirm
 ation signature after the talk - please print your own signature sheet bef
 orehand (71 kB pdf available for download here).
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://go.epfl.ch/
 EPFLBioETalks
STATUS:CONFIRMED
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