Nucleobindin-1: A Structural Analysis

Abstract

Objectives: Nucleobindins (NUCBs) are DNA and calcium binding, secreted proteins with various signaling functions. Two family members (NUCB1 and 2) were identified. Three peptides encoded within the NUCB2 could be processed by prohormone convertases. We recently identified a nesfatin-1-like peptide (NLP) encoded within the NUCB1. NLP suppressed feed intake in mice and fish, and stimulated insulin secretion from pancreatic beta cells. In this abstract we summarize similarities and differences in the amino acid sequence of NUCB1 across eukaryotes that results in their calcium and DNA binding property.

Methods: Annotated NUCB1 sequences were obtained from GenBank and sequence alignment was carried out using ClustalW and eBioX software. Percentage identity between sequences and functional domains were ascertained using ClustalW2 and X. Signal peptide and prohormone convertase cleavage site prediction was carried out using SignalP 4.1 and Prop 1. server, respectively.

Results: NUCB1 is a conserved protein family with five distinct sequence regions: (1) an N-terminal signal peptide (2) a putative neuropeptide region (3) a basic region that can bind to DNA (4) an EF-hand domain that consists of two EF-hand motifs and (5) a coiled-coil region that is a “leucine zipper” domain. In silico analysis showed the presence of enzyme cleavage sites located between a highly conserved region of 30 amino acids [M30] that could form the bioactive core of NLP.

Conclusions: NUCB1 is highly conserved in eukaryotes. Like nesfatin-1, NUCB1 encoded NLP contains a conserved bioactive core (M30) that could be secreted. This can account for its anorexigenic and insulinotropic action.