For these kind of issues, as an initial step, you need check the below details:
*Please confirm that the DNS records are set for the domain. Also it has been propagated.
*confirm that the rDNS entry for your main IP address is set which may cause this issue.
*If all those are Yes, then I would suggest switching off the SMTP Tweak and trying again. You can also try after restarting Exim. [/etc/init.d/exim restart]
*Any time you get 550 sender failed error you need to check your passwd and shadow permissions in /home/username/etc/domain.com they should be 644 and 640 respectively.