PXD019110

PXD019110 is an original dataset announced via ProteomeXchange.

Title	Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state
Description	Kindlin-1, -2, and -3, directly bind integrin β cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and link to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin β cytoplasmic tail as the integrin-binding pocket in the F3 sub-domain of one protomer is occluded by the PH domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells re-constituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared to those re-constituted with wild type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.
HostingRepository	PRIDE
AnnounceDate	2020-06-08
AnnouncementXML	Submission_2020-06-07_22:51:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SoFong Cam Ngan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-12 01:37:26	ID requested
⏵ 1	2020-06-07 22:51:53	announced

Dataset with its publication pending

submitter keyword: kindlin

FERM

fermitin

kindlin-3

integrin

extracellular matrix

DSSO

Siu Kwan Sze
contact affiliation	Nanyang Technological University
contact email	sksze@ntu.edu.sg
lab head
SoFong Cam Ngan
contact affiliation	Nanyang Technological University
contact email	sfcngan@ntu.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019110
     1. Label: PRIDE project
     2. Name: Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state