2HM6

Nematocyst outer wall antigen, NW1 G11V K21P

Summary for 2HM6

• Entry DOI: 10.2210/pdb2hm6/pdb
• Related: 2HM3 2HM4 2HM5
• Descriptor: Nematocyst outer wall antigen (1 entity in total)
• Functional Keywords: molecular evolution, cysteine rich, nematocyst, structural protein
• Biological source: Hydra vulgaris
• Total number of polymer chains: 1
• Total formula weight: 3090.45

Authors

Meier, S.,Jensen, P.R.,Grzesiek, S.,Oezbek, S. (deposition date: 2006-07-11, release date: 2007-02-06, Last modification date: 2024-11-13)

Primary citation

Meier, S.,Jensen, P.R.,David, C.N.,Chapman, J.,Holstein, T.W.,Grzesiek, S.,Ozbek, S.
Continuous molecular evolution of protein-domain structures by single amino Acid changes.
Curr.Biol., 17:173-178, 2007

PubMed Abstract: Protein structures cluster into families of folds that can result from extremely different amino acid sequences [1]. Because the enormous amount of genetic information generates a limited number of protein folds [2], a particular domain structure often assumes numerous functions. How new protein structures and new functions evolve under these limitations remains elusive. Molecular evolution may be driven by the ability of biomacromolecules to adopt multiple conformations as a bridge between different folds [3-6]. This could allow proteins to explore new structures and new tasks while part of the structural ensemble retains the initial conformation and function as a safeguard [7]. Here we show that a global structural switch can arise from single amino acid changes in cysteine-rich domains (CRD) of cnidarian nematocyst proteins. The ability of these CRDs to form two structures with different disulfide patterns from an identical cysteine pattern is distinctive [8]. By applying a structure-based mutagenesis approach, we demonstrate that a cysteine-rich domain can interconvert between two natively occurring domain structures via a bridge state containing both structures. Comparing cnidarian CRD sequences leads us to believe that the mutations we introduced to stabilize each structure reflect the birth of new protein folds in evolution.

PubMed: 17240343
DOI: 10.1016/j.cub.2006.10.063

Experimental method

SOLUTION NMR