Letters in high-end interdisciplinary journals – how much do they weigh in a CV? Are they only for experts?
Pretty much anything in a very high-end journal is difficult to get there and reflects a judgement on the part of the editors that your contribution will be of broad interest within the field.  Thus, it is likely to have a significant positive effect on your CV.

Moreover, depending on the journal the difference between "Letter" and "Article" is often of little significance.  For example, in Nature, the difference is that a Letter is 1500 words and an Article is 3000 words.  Since most Nature papers are really just the tip of a much larger iceberg of Supplementary Information in any case, this distinction doesn't really matter all that much, and probably few of your readers will even notice which of the formats your article is in.