Title : Structural determinants of natriuretic
peptide receptor specificity and degeneracy
Abstract :
- Cardiovascular homeostasis and blood pressure regulation are reliant, in part, on interactions between natriuretic peptide (NP) hormones and natriuretic peptide receptors ( NPR )
- The C-type NPR ( NPR-C ) is responsible for clearance of NP hormones from the circulation, and displays a cross-reactivity for all NP hormones ( ANP , BNP , and CNP ), in contrast to other NPRs, which are more restricted in their specificity
- In order to elucidate the structural determinants for the binding specificity and cross-reactivity of NPR-C with NP hormones, we have determined the crystal structures of the complexes of NPR-C with atrial natriuretic peptide ( ANP ), and with brain natriuretic peptide ( BNP )
- A structural comparison of these complexes, with the previous structure of the NPR-C / CNP complex, reveals that NPR-C uses a conformationally inflexible surface to bind three different, highly flexible, NP ligands
- The complex structures support a mechanism of rigid promiscuity rather than conformational plasticity by the receptor
- While ANP and BNP appear to adopt similar receptor-bound conformations, the CNP structure diverges, yet shares sets of common receptor contacts with the other ligands
- The degenerate versus selective hormone recognition properties of different NPRs appears to derive largely from two cavities on the receptor surfaces, pocket I and pocket II, that serve as anchoring sites for hormone side-chains and modulate receptor selectivity
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. peptide, , -, Structural determinants, peptide
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):