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DTSTART:20190331T030000
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DTSTART:20191027T020000
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BEGIN:VEVENT
DTSTAMP:20260406T024358Z
UID:5d8204eb9311d408337854@ist.ac.at
DTSTART:20190930T100000
DTEND:20190930T113000
DESCRIPTION:Speaker: Gayathri Singaraju\nhosted by Carl-Philipp Heisenberg\
 nAbstract: Cadherins mediate the cell-cell junctions in multicellular orga
 nisms. Essential cellular functions like cell-migration\, differentiation\
 , and morphogenesis that require tailoring of the cell-cell junctions are 
 achieved by regulating the expression of cadherins. Among cadherins\, non-
 classical cadherins comprise ~80% of cadherin proteins in the family. Howe
 ver\, little is known on their participation in cell-adhesion. Cadherin-23
  (Cdh23)\, long non-classical cadherin with 27 extracellular (EC) domains 
 has recently been known to mediate cell-cell junctions through homophilic 
 interactions\, and its expression is regulated during cancer metastasis. D
 ata from The Cancer Genome Atlas indicated a key correlation between Cdh23
  expression and patient survival\, lower the expression poor is the surviv
 al of patients. Further\, in-vitro studies have measured a stronger aggreg
 ation-propensity of Cdh23 than one of the typical cadherins. While the mec
 hanism of homophilic interaction for classical cadherins is known\, the ho
 modimer structure for Cdh23 is not yet resolved. We deciphered the unique 
 trans-homodimer structure of Cdh23 which consists of two electrostatic-bas
 ed interfaces extended up to two terminal domains (EC1-2). This unique int
 erface is robust with a dissociation constant\, 184 ?M and an off-rate of 
 ~8x10-4 s-1. Next\, we measured the role of the remaining 25 non-interacti
 ng EC-domains on the homophilic trans-interactions. With the help of domai
 n deletion mutants\, we showed that the flexibility exhibited by EC-domain
 s increases with the number of domains. In-cellulo aggregation assays also
  showed faster aggregation of cells with increasing domain numbers. From s
 ingle-molecule force spectroscopy studies\, we also observed that lifetime
  for the trans-interactions increases with the number of domains.
LOCATION:Meeting room 1st floor / Central Bldg. (I01.1OG - Zentralgebäude)
 \, ISTA
ORGANIZER:lalesch@ist.ac.at
SUMMARY:Gayathri Singaraju: Molecular mechanism of the cell-cell adhesion b
 y atypical cadherin-23
URL:https://talks-calendar.ista.ac.at/events/2168
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