Theresa May is to hold talks with Barack Obama and European leaders on a range of pressing global issues, including the threat posed by Islamic State (IS) fighters being pushed out of their Middle East strongholds.
Outgoing US president Mr Obama has been on a farewell trip to Europe, visiting Greece before arriving in Berlin for a meeting with the leaders of the UK, Germany, France, Italy and Spain.
The talks come against a backdrop of European nervousness about the election of Donald Trump as Mr Obama's successor in the White House following his criticism of Nato and scepticism about climate change.
Although Brexit is not on the agenda, Mrs May is also likely to discuss the situation with her European counterparts, including a one-to-one meeting with German Chancellor Angela Merkel.
French President Francois Hollande, Italian Prime Minister Matteo Renzi and Spanish counterpart Mariano Rajoy will also be at the meeting in the German capital.
A Downing Street spokesman said the main item on the agenda would be IS, also known as Daesh, with concerns about the dispersal of battle-hardened terrorists forced out of Iraq and Syria in the face of coalition attacks.
The issue of the movement of IS fighters was raised at the UN General Assembly (UNGA) meeting in September and will be discussed again.
"The issue that was raised at UNGA and will be raised here again is the issue of them being dispersed around other countries in Africa and parts of the Middle East, not specifically back to the UK," the spokesman said.
"As we close down Daesh's areas of operation in one part of the world we need to be mindful of the fact that they may regroup in other parts and how we set about tackling that.
"Obviously, the issue of Daesh fighters who've been in either Syria or Iraq returning to Europe is a matter of grave concern."
Russia's "increasingly assertive stance in Eastern Europe and around the world" will also be discussed.
The US, UK, France, Germany and Italy make up the so-called "Quint" group of Nato allies.
Mr Trump has expressed reservations about Nato and the commitment to mutual self-defence, criticising members of the alliance for their lack of defence spending.
Asked about the US commitment to Nato, the Downing Street spokesman said: "We are very clear on the importance of Nato as a cornerstone of European defence.
"We remain committed to it and our partners remain committed to it as well."
The UK was "committed" to ensuring that other members met the target of spending 2% of GDP on defence, but the issue was not specifically on the agenda for the Berlin talks.
The spokesman said the subject of Brexit was "not on the agenda" but added that "in the margins of the meeting almost certainly it will crop up in discussion".
The bilateral meeting with Mrs Merkel "will likely feature security issues", he said, adding: "It will be a wide-ranging discussion.
"Brexit will be part of it, I'm sure."
Asked whether ongoing sanctions on Russia would be discussed in Berlin, the Downing Street spokesman said: "Clearly we will seek agreement to maintain the Ukraine-related sanctions until such time as we see the Minsk Agreement implemented.
"Obviously, we will expect to see the Quint leaders united in the need to keep up pressure on the Syrian regime and their influencers to stop the actions that are taking place there.
"Discussions between Quint leaders have been taking place for some time. You've seen a united response every time we've had these discussions and we would expect that there will be agreement in Berlin that it's important we keep the pressure up and work together to find the kind of space that will create a peaceful resolution to the situation in Syria."