Nature sub-journal: PAPP-A three-dimensional structure

The growth factor IGF plays a key role
in the human growth process.
In the absence of an IGF signal, we become short.

Later in life, IGFs are involved in age-related diseases such as cancer and cardiovascular disease
.
In both cases, the IGF must be converted from the inactive form to the active form
.
This is exactly what
Popp-A is able to do.

"Seven years ago, we discovered that the STC2 protein blocks the activity of PAPP-A and therefore indirectly inhibits the activity
of IGF growth factor.
To block activity, STC2 must form a complex with ppap-a
.
We studied the complex, and now we know its three-dimensional structure
.
We know a lot about biochemistry, and it's interesting
to see what molecules actually look like.
PAPP-A is heart-shaped with a "cavity"
inside.
But from a research point of view, shape is not the most interesting feature
.
Rather, it is an interaction between different elements in the molecule," explains Professor Klaus Oxweig
.

There are still many unanswered mysteries
about the molecular mechanisms that regulate how much IGF is converted to the active form.
The composite formation between PAPP-A and STC2 is likely to be highly regulated
.
This hypothesis is supported by earlier studies that suggest that natural variants of human STC2, in which only one amino acid is replaced, are slightly slower
to form complexes with PAPP-A.
The result is that slightly more IGF can be activated by ppap-a, resulting in a height increase of 2.
1 cm
.

Report PAPP-A· The first author of the publication STC2 structure was graduate student Sara Dam Kobber?, who used cryo-electron microscopy (cryo-EM) to determine the structure of
large protein complexes.
Denmark's National Cryo-Electron Microscopy Research Infrastructure (EMBION, AU) approved the study, with participants from the University of Copenhagen also
participating.