PMID- 10371151
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20191210
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 451
IP  - 2
DP  - 1999 May 21
TI  - NMR structure of a minimized human agouti related protein prepared by total
      chemical synthesis.
PG  - 125-31
AB  - The structure of the chemically synthesized C-terminal region of the human agouti
      related protein (AGRP) was determined by 2D 1H NMR. Referred to as minimized
      agouti related protein, MARP is a 46 residue polypeptide containing 10 Cys
      residues involved in five disulfide bonds that retains the biological activity of
      full length AGRP. AGRP is a mammalian signaling molecule, involved in weight
      homeostasis, that causes adult onset obesity when overexpressed in mice. AGRP was
      originally identified by homology to the agouti protein, another potent signaling
      molecule involved in obesity disorders in mice. While AGRP's exact mechanism of
      action is unknown, it has been identified as a competitive antagonist of
      melanocortin receptors 3 and 4 (MC3r, MC4r), and MC4r in particular is implicated
      in the hypothalamic control of feeding behavior. Full length agouti and AGRP are 
      only 25% homologous, however, their active C-terminal regions are approximately
      40% homologous, with nine out of the 10 Cys residues spatially conserved. Until
      now, 3D structures have not been available for either agouti, AGRP or their
      C-terminal regions. The NMR structure of MARP reported here can be characterized 
      as three major loops, with four of the five disulfide bridges at the base of the 
      structure. Though its fold is well defined, no canonical secondary structure is
      identified. While previously reported structural models of the C-terminal region 
      of AGRP were attempted based on Cys homology between AGRP and certain toxin
      proteins, we find that Cys spacing is not sufficient to correctly determine the
      3D fold of the molecule.
FAU - Bolin, K A
AU  - Bolin KA
AD  - Department of Chemistry and Biochemistry, University of California, Santa Cruz
      95064, USA.
FAU - Anderson, D J
AU  - Anderson DJ
FAU - Trulson, J A
AU  - Trulson JA
FAU - Thompson, D A
AU  - Thompson DA
FAU - Wilken, J
AU  - Wilken J
FAU - Kent, S B
AU  - Kent SB
FAU - Gantz, I
AU  - Gantz I
FAU - Millhauser, G L
AU  - Millhauser GL
LA  - eng
GR  - GM46870/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (AGRP protein, human)
RN  - 0 (ASIP protein, human)
RN  - 0 (Agouti Signaling Protein)
RN  - 0 (Agouti-Related Protein)
RN  - 0 (Agrp protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (a protein, mouse)
SB  - IM
MH  - Agouti Signaling Protein
MH  - Agouti-Related Protein
MH  - Amino Acid Sequence
MH  - Animals
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Magnetic Resonance Spectroscopy
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Molecular Structure
MH  - Multigene Family
MH  - Protein Structure, Tertiary
MH  - Proteins/*chemical synthesis/*chemistry/classification
EDAT- 1999/06/17 00:00
MHDA- 1999/06/17 00:01
CRDT- 1999/06/17 00:00
PHST- 1999/06/17 00:00 [pubmed]
PHST- 1999/06/17 00:01 [medline]
PHST- 1999/06/17 00:00 [entrez]
AID - S0014-5793(99)00553-0 [pii]
AID - 10.1016/s0014-5793(99)00553-0 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 May 21;451(2):125-31. doi: 10.1016/s0014-5793(99)00553-0.