2KA1

Solution NMR structure of BNIP3 transmembrane peptide dimer in detergent micelles

Summary for 2KA1

• Entry DOI: 10.2210/pdb2ka1/pdb
• Related: 2KA2
• NMR Information: BMRB: 16012
• Descriptor: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (1 entity in total)
• Functional Keywords: integral membrane protein, membrane helix-helix interactions, bnip3, transmembrane domain, homodimer, membrane protein folding, apoptosis, host-virus interaction, mitochondrion, phosphoprotein, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 7581.18

Authors

Sulistijo, E.S.,MacKenzie, K.R. (deposition date: 2008-10-30, release date: 2009-06-23, Last modification date: 2024-05-08)

Primary citation

Sulistijo, E.S.,Mackenzie, K.R.
Structural basis for dimerization of the BNIP3 transmembrane domain
Biochemistry, 48:5106-5120, 2009

PubMed Abstract: Mutagenesis data suggest that BNIP3 transmembrane domain dimerization depends critically on hydrogen bonding between His 173 and Ser 172, but a recent structural analysis indicates that these residues adopt multiple conformations and are not always hydrogen bonded. We show that in dodecylphosphocholine micelles the structure of the BNIP3 transmembrane domain is modulated by phospholipids and that appropriate reconstitution and lipid titration yield a single set of peptide resonances. NMR structure determination reveals a symmetric dimer in which all interfacial residues, including His 173 and Ser 172, are well-defined. Small residues Ala 176, Gly 180, and Gly 184 allow close approach of essentially ideal helices in a geometry that supports intermonomer hydrogen bond formation between the side chains of His 173 and Ser 172. Bulky residues Ile 177 and Ile 181 pack against small residues of the opposite monomer, and favorable polar backbone-backbone contacts at the interface likely include noncanonical Calpha-H.O=C hydrogen bonds from Gly 180 to Ile 177. Modeling mutations into the structure shows that most deleterious hydrophobic substitutions eliminate the His-Ser hydrogen bond or introduce an intermonomer clash, indicating critical roles for sterics and hydrogen bonding in the sequence dependence of dimerization. Substitutions at most noninterfacial positions do not alter dimerization, but the disruptive effects of substitutions at Ile 183 cannot be rationalized in terms of peptide-peptide contacts and therefore may indicate a role for peptide-detergent or peptide-lipid interactions at this position.

PubMed: 19415897
DOI: 10.1021/bi802245u

Experimental method

SOLUTION NMR