Comparative 2D NMR studies of human insulin and des-pentapeptide insulin: Sequential resonance assignment and implications for protein dynamics and receptor recognition

Journal Article · Tue Jun 04 04:00:00 EDT 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00236a025· OSTI ID:5081219

Hua, Qingxin ^[1]; Weiss, M A ^[2]

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1. Harvard Medical School, Boston, MA (United States)
2. Harvard Medical School, Boston, MA (United States) Massachusetts General Hospital, Boston, MA (United States)

The solution structure and dynamics of human insulin are ivestigated by 2D {sup 1}H NMR spectroscopy in reference to a previously analyzed analogue, des-pentapeptide (B26-B30) insulin. This spectroscopic comparison is of interest since (i) the structure of the C-terminal region of the B-chain has not been determined in the monomeric state and (ii) the role of this region in binding to the insulin receptor has been the subject of long-standing speculation. The present NMR studies are conducted in the presence of an organic cosolvent (20% acetic acid), under which conditions both proteins are monomeric and stably folded. Complete sequential assignment of human insulin is obtained and leads to the following conclusions. (1) The secondary structure of the insulin monomer (three {alpha}-helices and B-chain {beta}-turn) is similar to that observed in the 2-Zn crustal state. (2) The folding of DPI is essentially the same as the corresponding portion of intact insulin, in accord with the similarities between their respective crystal structues. (3) residues B24-B28 adopt an extended configuration in the monomer and pack against the hydrophobic core as in crystallographic dimers; residues B29 and B30 are largely disordered. (4) The insulin fold is shown to provide a model for collective motions in a protein with implications for the mechanism of protein-protein recognition. To their knowledge, this paper describes the first detailed analysis of a protein NMR spectrum under conditions of extensive conformational broadening.

• OSTI ID: 5081219
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:22; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AQUEOUS SOLUTIONS
BARYONS
BIOPHYSICS
DISPERSIONS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HORMONES
INSULIN
MAGNETIC RESONANCE
MEMBRANE PROTEINS
MIXTURES
NUCLEAR MAGNETIC RESONANCE
NUCLEONS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PEPTIDES
PROTEIN STRUCTURE
PROTEINS
PROTONS
RECEPTORS
RESONANCE
SOLUTIONS